Cyclic malonamides as inhibitors of a beta protein production

ABSTRACT

This invention relates to novel cyclic malonamides having the formula (I):  
                 
 
     to their pharmaceutical compositions and to their methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of Aβ-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to β-amyloid production such as Alzheimer&#39;s disease and Down&#39;s Syndrome.

FIELD OF THE INVENTION

[0001] This invention relates to novel cyclic malonamides having drugand bio-affecting properties, their pharmaceutical compositions andmethods of use. These novel compounds inhibit the processing of amyloidprecursor protein and, more specifically, inhibit the production ofAP-peptide, thereby acting to prevent the formation of neurologicaldeposits of amyloid protein. More particularly, the present inventionrelates to the treatment of neurological disorders related to β-amyloidproduction such as Alzheimer's disease and Down's Syndrome.

BACKGROUND OF THE INVENTION

[0002] Alzheimer's disease (AD) is a degenerative brain disordercharacterized clinically by progressive loss of memory, temporal andlocal orientation, cognition, reasoning, judgment and emotionallystability. AD is a common cause of progressive dementia in humans and isone of the major causes of death in the United States. AD has beenobserved in all races and ethnic groups worldwide, and is a majorpresent and future health problem. No treatment that effectivelyprevents AD or reverses the clinical symptoms and underlyingpathophysiology is currently available (for review, Dennis J. Selkoe;Cell Biology of the amyloid (beta)-protein precursor and the mechanismof Alzheimer's disease, Annu Rev Cell Biol, 1994, 10: 373-403).

[0003] Histopathological examination of brain tissue derived uponautopsy or from neurosurgical specimens in effected individuals revealedthe occurrence of amyloid plaques and neurofibrillar tangles in thecerebral cortex of such patients. Similar alterations were observed inpatients with Trisomy 21 (Down's syndrome), and hereditary cerebralhemorrhage with amyloidosis of the Dutch-type. Neurofibrillar tanglesare nonmembrane-bound bundles of abnormal proteinaceous filaments andbiochemical and immunochemical studies led to the conclusion that theirprinciple protein subunit is an altered phosphorylated form of the tauprotein (reviewed in Selkoe, 1994).

[0004] Biochemical and immunological studies revealed that the dominantproteinaceous component of the amyloid plaque is an approximately 4.2kilodalton (kD) protein of about 39 to 43 amino acids. This protein wasdesignated Aβ, β-amyloid peptide, and sometimes β/A4; referred to hereinas Aβ. In addition to its deposition in amyloid plaques, Aβ is alsofound in the walls of meningeal and parenchymal arterioles, smallarteries, capillaries, and sometimes, venules. Aβ was first purified anda partial amino acid reported in 1984 (Glenner and Wong, Biochem.Biophys. Res. Commun. 120: 885-890). The isolation and sequence data forthe first 28 amino acids are described in U.S. Pat. No 4,666,829.

[0005] Compelling evidence accumulated during the last decade revealedthat Aβ is an internal polypeptide derived from a type 1 integralmembrane protein, termed β amyloid precursor protein (APP). β APP isnormally produced by many cells both in vivo and in cultured cells,derived from various animals and humans. Aβ is derived from cleavage ofβ APP by as yet unknown enzyme (protease) system(s), collectively termedsecretases.

[0006] The existence of at least four roteolytic activities has beenpostulated. They include β secretase(s), generating the N-terminus ofAβ, α secretase(s) cleaving around the 16/17 peptide bond in Aβ, and γsecretases, generating C-terminal Aβ fragments ending at position 38,39, 40, 42, and 43 or generating C-terminal extended precursors whichare subsequently truncated to the above polypeptides.

[0007] Several lines of evidence suggest that abnormal accumulation ofAβ plays a key role in the pathogenesis of AD. Firstly, Aβ is the majorprotein found in amyloid plaques. Secondly, Aβ is neurotoxic and may becausally related to neuronal death observed in AD patients. Thirdly,missense DNA mutations at position 717 in the 770 isoform of β APP canbe found in effected members but not unaffected members of severalfamilies with a genetically determined (familiar) form of AD. Inaddition, several other β APP mutations have been described in familiarforms of AD. Fourthly, similar neuropathological changes have beenobserved in transgenic animals overexpressing mutant forms of human βAPP. Fifthly, individuals with Down's syndrome have an increased genedosage of β APP and develop early-onset AD. Taken together, theseobservations strongly suggest that Aβ depositions may be causallyrelated to the AD.

[0008] It is hypothesized that inhibiting the production of Aβ willprevent and reduce neurological degeneration, by controlling theformation of amyloid plaques, reducing neurotoxicity and, generally,mediating the pathology associated with Aβ production. One method oftreatment methods would therefore be based on drugs that inhibit theformation of Aβ in vivo.

[0009] Methods of treatment could target the formation of Aβ through theenzymes involved in the proteolytic processing of β amyloid precursorprotein. Compounds that inhibit β or γ secretase activity, eitherdirectly or indirectly, could control the production of Aβ.Advantageously, compounds that specifically target γ secretases, couldcontrol the production of Aβ. Such inhibition of β or γ secretases couldthereby reduce production of Aβ, which, thereby, could reduce or preventthe neurological disorders associated with Aβ protein.

[0010] PCT publication number WO 96/29313 discloses the general formula:

[0011] covering metalloprotease inhibiting compounds useful for thetreatment of diseases associated with excess and/or unwanted matrixmetalloprotease activity, particularly collagenase and or stromelysinactivity.

[0012] Compounds of general formula:

[0013] are disclosed in PCT publication number WO 95/22966 relating tomatrix metalloprotease inhibitors. The compounds of the invention areuseful for the treatment of conditions associated with the destructionof cartilage, including corneal ulceration, osteoporosis, periodontitisand cancer.

[0014] European Patent Application number EP 0652009A1 relates to thegeneral formula:

[0015] and discloses compounds that are protease inhibitors that inhibitAβ production.

[0016] U.S. Pat. No. 5,703,129 discloses the general formula:

[0017] which covers 5-amino-6-cyclohexyl-4-hydroxy-hexanamidederivatives that inhibit Aβ production and are useful in the treatmentof Alzheimer's disease.

[0018] Copending, commonly assigned U.S. patent application Ser. No.09/370089 filed Aug. 7, 1999 (equivalent to international applicationPCT US99/17717) discloses lactams of general formula:

[0019] wherein the lactam ring B is substituted by succinamide and acarbocyclic, aryl, or heteroaryl group. These compounds inhibit theprocessing of amyloid precursor protein and, more specifically, inhibitthe production of Aβ-peptide, thereby acting to prevent the formation ofneurological deposits of amyloid protein.

[0020] None of the above references teaches or suggests the compounds ofthe present invention which are described in detail below.

SUMMARY OF THE INVENTION

[0021] One object of the present invention is to provide novel compoundswhich are useful as inhibitors of the production of Aβ protein orpharmaceutically acceptable salts or prodrugs thereof.

[0022] It is another object of the present invention to providepharmaceutical compositions comprising a pharmaceutically acceptablecarrier and a therapeutically effective amount of at least one of thecompounds of the present invention or a pharmaceutically acceptable saltor prodrug form thereof.

[0023] It is another object of the present invention to provide a methodfor treating degenerative neurological disorders comprisingadministering to a host in need of such treatment a therapeuticallyeffective amount of at least one of the compounds of the presentinvention or a pharmaceutically acceptable salt or prodrug form thereof.

[0024] These and other objects, which will become apparent during thefollowing detailed description, have been achieved by the inventors'discovery that compounds of Formula (I):

[0025] or a stereoisomer, pharmaceutically acceptable salt or prodrugforms thereof, wherein R³, R⁶, B, C, W, X, Y, and Z are defined below,are effective inhibitors of the production of Aβ.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0026] Thus, in a first embodiment, the present invention provides anovel compound of Formula (I):

[0027] or a stereoisomer, pharmaceutically acceptable salt or prodrugthereof, wherein:

[0028] L is —NR²⁶C(═O)—, —C(═O)NR²⁶—, —NR²⁶C(═O)O—, —OC(═O)NR²⁶, or—NR²⁶C (═O)NR²⁶—;

[0029] R³ is —(CR⁷R^(7a))_(n)—R⁴, —(CR⁷R^(7a))_(l)—S—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—O—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—S(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—S(═O)₂—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—C(═O)—(CR⁷R^(7a))_(m)—R⁴, —(CR⁷R^(7a))_(l)—N(R^(7b))C(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—C(═O)N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—N(R^(7b))S(═O)₂—(CR⁷R^(7a))_(m)—R⁴, or—(CR⁷R^(7a))_(l)—S(═O)₂N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴;

[0030] n is 0, 1, 2, or 3;

[0031] m is 0, 1, 2, or 3;

[0032] l is 1, 2, or 3;

[0033] Ring C is a 3 to 8 membered carbocycle,

[0034] wherein the carbocycle is saturated or partially saturated;

[0035] optionally, the carbocycle contains a heteroatom selected from—O—, —S—, —S(═O)—, —S(═O)₂—, and —N(R²⁰)—; and

[0036] wherein the carbocycle is substituted with 0-4 R²¹;

[0037] R⁴ is H, OH, OR^(14a),

[0038] C₁-C₈ alkyl substituted with 0-3 R^(4a),

[0039] C₂-C₈ alkenyl substituted with 0-3 R^(4a),

[0040] C₂-C₈ alkynyl substituted with 0-3 R^(4a),

[0041] C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),

[0042] C₆-C₁₀ aryl substituted with 0-3 R^(4b), or

[0043] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(4b);

[0044] R^(4a), at each occurrence, is independently selected from H, OH,F, Cl, Br, I, NR¹⁵R¹⁶, CF₃,

[0045] C₃-C₁₀ carbocycle substituted with 0-3 R_(4b),

[0046] C₆-C₁₀ aryl substituted with 0-3 R_(4b), and

[0047] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(4b);

[0048] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0049] R⁶ is H;

[0050] C₁-C₆ alkyl substituted with 0-3 R^(6a);

[0051] C₃-C₁₀ carbocycle substituted with 0-3 R^(6b); or

[0052] C₆-C₁₀ aryl substituted with 0-3 R^(6b);

[0053] R^(6a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, aryl and CF₃;

[0054] R^(6b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R₁₆, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, and C₁-C₄ haloalkoxy;

[0055] R⁷, at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, CF₃, C₁-C₄ alkyl, phenyl substituted with 0-5 R^(7c);

[0056] R^(7a), at each occurrence, is independently selected from H, Cl,F, Br, I, CN, CF₃, and C₁-C₄ alkyl;

[0057] R^(7b) is independently selected from H and C₁-C₄ alkyl;

[0058] R^(7c), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, CF₃, C₁-C₄ alkoxy, and C₁-C₄ alkyl;

[0059] B is a 5 to 10 membered lactam,

[0060] wherein the lactam is saturated, partially saturated orunsaturated;

[0061] wherein each additional lactam carbon is substituted with 0-2R¹¹; and,

[0062] optionally, the lactam contains an additional heteroatom selectedfrom —O—, —S—, —S(═O)—, —S(═O)₂—, —N═, —NH—, and —N(R¹⁰)—;

[0063] R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,S(═O)₂R¹⁷;

[0064] C₁-C₆ alkyl optionally substituted with 0-3 R^(10a);

[0065] C₆-C₁₀ aryl substituted with 0-4 R^(10b);

[0066] C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or

[0067] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(10b);

[0068] R^(10a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, arylsubstituted with 0-4 R^(13b); C₃-C₁₀ carbocycle substituted with 0-3R^(10b), and 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(10b);

[0069] R^(10b), at each occurrence, is independently selected from H,OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

[0070] R¹¹, at each occurrence, is independently selected from H, C₁-C₄alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;

[0071] C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);

[0072] C₆-C₁₀ aryl substituted with 0-3 R^(11b);

[0073] C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); and

[0074] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(11b);

[0075] R^(11a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃;

[0076] phenyl substituted with 0-3 R^(11b);

[0077] C₃-C₆ cycloalkyl substituted with 0-3 R^(11b); and

[0078] 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(11b);

[0079] R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0080] additionally, two R¹¹ substituents on adjacent atoms may becombined to form a 5 to 6 membered heteroaryl fused radical, whereinsaid 5 to 6 membered heteroaryl fused radical comprises 1 or 2heteroatoms selected from N, O, and S; wherein said 5 to 6 memberedheteroaryl fused radical is substituted with 0-3 R¹³;

[0081] additionally, two R¹¹ substituents on the same or adjacent carbonatoms may be combined to form a C₃-C₆ carbocycle substituted with 0-3R¹³;

[0082] additionally, two R¹¹ substituents on adjacent atoms may becombined to form a benzo fused radical; wherein said benzo fused radicalis substituted with 0-4 R¹³;

[0083] W is —(CR⁸R^(8a))_(p)—;

[0084] p is 0, 1, 2, 3, or 4;

[0085] R⁸ and R^(8a), at each occurrence, are independently selectedfrom H, F, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl and C₃-C₈cycloalkyl;

[0086] X is a bond;

[0087] C₆-C₁₀ aryl substituted with 0-3 R^(Xb);

[0088] C₃-C₁₀ carbocycle substituted with 0-3 R^(Xb); or

[0089] 5 to 10 membered heterocycle substituted with 0-2 R^(Xb);

[0090] R^(Xb), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄halothioalkoxy;

[0091] Y is a bond or (CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—;

[0092] t is 0, 1, 2, or 3;

[0093] u is 0, 1, 2, or 3;

[0094] R⁹ and R^(9a), at each occurrence, are independently selectedfrom H, F, C₁-C₆ alkyl and C₃-C₈ cycloalkyl;

[0095] V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,—C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—,—NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C—(═O)O—, or —OC(═O)—;

[0096] Z is H;

[0097] C₁-C₈ alkyl substituted with 1-3 R¹²;

[0098] C₂-C₄ alkenyl substituted with 1-3 R¹²;

[0099] C₂-C₄ alkynyl substituted with 1-3 R¹²;

[0100] C₁-C₈ alkyl substituted with 0-3 R^(12a);

[0101] C₂-C₄ alkenyl substituted with 0-3 R^(12a);

[0102] C₂-C₄ alkynyl substituted with 0-3 R^(12a);

[0103] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0104] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0105] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0106] R¹², at each occurrence, is independently selected from C₆-C₁₀aryl substituted with 0-4 R^(12b);

[0107] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and

[0108] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0109] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄haloalkoxy, and C₁-C₄ haloalkyl-S—;

[0110] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0111] R¹³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

[0112] R¹⁴ is H, phenyl substituted with 0-4 R^(14b), benzyl substitutedwith 0-4 R^(14b), C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆ cycloalkyl;

[0113] R^(14a)is H, C₆-C₁₀ aryl, benzyl, heterocycle, or C₁-C₄ alkyl;

[0114] R^(14b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0115] R¹⁵, at each occurrence, is independently selected from H, C₁-C₆alkyl, aryl-(C₁-C₆ alkyl)- wherein the aryl is substituted with 0-4R^(15b), (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—;

[0116] R^(15b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0117] R¹⁶, at each occurrence, is independently selected from H, C₁-C₆alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0118] R¹⁷ is H, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, aryl substituted by 0-4R^(17a), or —CH₂-aryl substituted by 0-4 R^(17a);

[0119] R^(17a) is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃, S(O)CH₃, SO₂CH₃,—NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl;

[0120] R¹⁸, at each occurrence, is independently selected from H, C₁-C₆alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0121] R¹⁹, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0122] R²⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,S(═O)₂R¹⁷;

[0123] C₁-C₆ alkyl optionally substituted with 0-2 R^(20a);

[0124] C₆-C₁₀ aryl substituted with 0-4 R^(20b);

[0125] C₃-C₁₀ carbocycle substituted with 0-3 R^(20b); or

[0126] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(20b);

[0127] R^(20a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, F, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, aryl substituted with0-4 R^(20b), and heterocycle substituted with 0-4 R^(20b);

[0128] R^(20b), at each occurrence, is independently selected from H,OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

[0129] R²¹, at each occurrence, is independently selected from H, C₁-C₄alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;

[0130] C₁-C₆ alkyl optionally substituted with 0-3 R^(21a);

[0131] C₆-C₁₀ aryl substituted with 0-3 R^(21b);

[0132] C₃-C₁₀ carbocycle substituted with 0-3 R^(21b); and

[0133] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(21b);

[0134] R^(21a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃;

[0135] phenyl substituted with 0-3 R^(21b);

[0136] C₃-C₆ cycloalkyl substituted with 0-3 R^(21b); and

[0137] 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(21b);

[0138] R^(21b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—

[0139] additionally, two R²¹ substituents on adjacent atoms may becombined to form a 5 to 6 membered heteroaryl fused radical, whereinsaid 5 to 6 membered heteroaryl fused radical comprises 1 or 2heteroatoms selected from N, O, and S; wherein said 5 to 6 memberedheteroaryl fused radical is substituted with 0-3 R²³;

[0140] additionally, two R²¹ substituents on the same or adjacent carbonatoms may be combined to form a C₃-C₆ carbocycle substituted with 0-3R²³;

[0141] additionally, two R²¹ substituents on adjacent atoms may becombined to form a benzo fused radical; wherein said benzo fused radicalis substituted with 0-4 R²³;

[0142] R²³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

[0143] R²⁶ is H;

[0144] C₁-C₆ alkyl substituted with 0-3 R^(26a);

[0145] C₃-C₁₀ carbocycle substituted with 0-3 R^(26b); or

[0146] C₆-C₁₀ aryl substituted with 0-3 R^(26b);

[0147] R^(26a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, aryl and CF₃; and

[0148] R^(26b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy.

[0149] [2] In a preferred embodiment the present invention provides acompound of Formula (I), wherein:

[0150] L is —NR²⁶C(═O)—, —C(═O)NR²⁶—, or —OC(═O)NR²⁶—;

[0151] R³ is —(CHR⁷)_(n)—R⁴, —(CHR⁷)_(l)—N—(CR⁷R^(7a))_(m)—R⁴, or—(CHR⁷)_(l)—O—(CR⁷R^(7a))_(m)—R⁴;

[0152] n is 0, 1 or 2;

[0153] m is 0, 1 or 2;

[0154] l is 1;

[0155] Ring C is a 3 to 8 membered carbocycle substituted with 0-4 R²¹;optionally, the carbocycle contains a heteroatom selected from 13 O— and—N(R²⁰)—;

[0156] R⁴ is H, OH, OR^(14a),

[0157] C₁-C₆ alkyl substituted with 0-3 R^(4a),

[0158] C₂-C₆ alkenyl substituted with 0-2 R^(4a),

[0159] C₂-C₆ alkynyl substituted with 0-1 R^(4a),

[0160] C₃-C₆ carbocycle substituted with 0-3 R^(4b),

[0161] C₆-C₁₀ aryl substituted with 0-3 R^(4b), or

[0162] 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b);

[0163] R^(4a), at each occurrence, is independently selected from H, OH,F, Cl, Br, I, NR¹⁵R¹⁶, CF₃,

[0164] C₃-C₆ carbocycle substituted with 0-3 R^(4b),

[0165] phenyl substituted with 0-3 R^(4b), and

[0166] 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b);

[0167] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

[0168] R⁶ is H;

[0169] R⁷, at each occurrence, is independently selected from H, OH, F,CF₃, methyl, and ethyl;

[0170] Ring B is a 7 membered lactam,

[0171] wherein the lactam is saturated, partially saturated orunsaturated;

[0172] wherein each additional lactam carbon is substituted with 0-2R¹¹; and,

[0173] optionally, the lactam contains a heteroatom selected from —O—,—S—, —S(═O)—, —S(═O)₂—, —N═, —NH—, and —N(R¹⁰)—;

[0174] R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,S(═O)₂R¹⁷;

[0175] C₁-C₆ alkyl optionally substituted with 0-2 R^(10a);

[0176] C₆-C₁₀ aryl substituted with 0-4 R^(10b);

[0177] C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or

[0178] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(10b);

[0179] R^(10a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl , F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, phenylsubstituted with 0-4 R^(10b); and 5 to 10 membered heterocyclecontaining 1 to 4 heteroatoms selected from nitrogen, oxygen, andsulphur, wherein said 5 to 10 membered heterocycle is substituted with0-3 R^(10b);

[0180] R^(10b), at each occurrence, is independently selected from H,OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, C, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

[0181] R¹¹, at each occurrence, is independently selected from H, C₁-C₄alkoxy, C, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;

[0182] C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);

[0183] C₆-C₁₀ aryl substituted with 0-3 R^(11b);

[0184] C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); and

[0185] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(11b);

[0186] R^(11a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenylsubstituted with 0-3 R^(11b);

[0187] R^(11b), at each occurrence, is independently selected from H,OH, C, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄haloalkoxy;

[0188] additionally, two R¹¹ substituents on adjacent atoms may becombined to form a benzo fused radical; wherein said benzo fused radicalis substituted with 0-2 R¹³;

[0189] additionally, two R¹¹ substituents on adjacent atoms may becombined to form a 5 to 6 membered heteroaryl fused radical, whereinsaid 5 to 6 membered heteroaryl fused radical comprises 1 or 2heteroatoms selected from N, O, and S; wherein said 5 to 6 memberedheteroaryl fused radical is substituted with 0-2 R¹³;

[0190] additionally, two R¹¹ substituents on the same or adjacent carbonatoms may be combined to form a C₃-C₆ carbocycle substituted with 0-2R¹³;

[0191] W is a bond, —CH₂—, —CH(CH₃)—, —CH₂CH₂— or —CH(CH₃)CH₂—;

[0192] X is a bond;

[0193] phenyl substituted with 0-2 R^(Xb);

[0194] C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or

[0195] 5 to 6 membered heterocycle substituted with 0-2 R^(Xb);

[0196] R^(Xb), at each occurrence, is independently selected from H, OH,Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

[0197] Y is a bond, —CH₂—V—, —V—, or —V—CH₂—;

[0198] V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—,—N(CH₃)—, or —N(CH₂CH₃)—,

[0199] Z is H; C₁-C₆ alkyl; C₂-C₄ alkenyl; C₂-C₄ alkynyl;

[0200] C₁-C₃ alkyl substituted with 1-2 R¹²;

[0201] C₂-C₃ alkenyl substituted with 1-2 R¹²;

[0202] C₂-C₃ alkynyl substituted with 1-2 R¹²;

[0203] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0204] C₃-C₆ carbocycle substituted with 0-3 R^(12b); or

[0205] 5 to 10 membered heterocycle substituted with 0-3 R^(12b);

[0206] R¹², at each occurrence, is independently selected from C₆-C₁₀aryl substituted with 0-4 R^(12b);

[0207] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and

[0208] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0209] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0210] R¹³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

[0211] R¹⁴ is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl;

[0212] R^(14a) is H, phenyl, benzyl, or C₁-C₄ alkyl;

[0213] R¹⁵, at each occurrence, is independently selected from H, C₁-C₄alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄alkyl)-S(═O)₂—;

[0214] R¹⁶, at each occurrence, is independently selected from H, OH,C₁-C₄ alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄alkyl)-S(═O)₂—;

[0215] R¹⁷ is H, methyl, ethyl, propyl, butyl, methoxymethyl,ethoxymethyl, methoxyethyl, ethoxyethyl, phenyl substituted by 0-3R^(17a), or —CH₂-phenyl substituted by 0-3 R^(17a);

[0216] R^(17a) is H, methyl, methoxy, —OH, F, Cl, CF₃, or OCF₃;

[0217] R¹⁸, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

[0218] R¹⁹, at each occurrence, is independently selected from H,methyl, and ethyl;

[0219] R²⁰ is H or C(═O)OR¹⁷;

[0220] R²⁶ is H, methyl, or ethyl.

[0221] [3] In another preferred embodiment the present inventionprovides a compound of Formula (I), wherein:

[0222] Ring C is selected from:

[0223]  wherein Ring C is substituted with 0-2 R²¹; and

[0224] Ring B is selected from:

[0225] [4] In another more preferred embodiment the present inventionprovides a compound of Formula (I), wherein:

[0226] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0227] R³ is R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

[0228] R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenylsubstituted with 0-1 R^(4a), or C₂-C₆ alkynyl substituted with 0-1R^(4a);

[0229] R^(4a), at each occurrence, is independently selected from H, OH,F, NR¹⁵R¹⁶, CF₃,

[0230] C₃-C₆ carbocycle substituted with 0-3 R^(4b),

[0231] phenyl substituted with 0-3 R^(4b), and

[0232] 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b); wherein said 5 to 6membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl,furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl,pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;

[0233] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl,propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂haloalkoxy;

[0234] W is a bond, —CH₂—, —CH(CH₃)—, —CH₂CH₂— or —CH(CH₃)CH₂—;

[0235] X is a bond, phenyl, C₃-C₆ cycloalkyl, or 5 to 6 memberedheterocycle;

[0236] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—,—N(CH₃)—, or —N(CH₂CH₃)—,

[0237] Z is H; C₁-C₆ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl,

[0238] C₁-C₃ alkyl substituted with 1-2 R¹²;

[0239] C₂-C₃ alkenyl substituted with 1-2 R¹²;

[0240] C₂-C₃ alkynyl substituted with 1-2 R¹²;

[0241] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0242] C₃-C₆ carbocycle substituted with 0-3 R^(12b); or

[0243] 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(12b); wherein said 5 to6 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, andtetrazolyl;

[0244] R¹² at each occurrence, is independently selected from C₆-C₁₀aryl substituted with 0-4 R^(12b);

[0245] C₃-C₆ carbocycle substituted with 0-3 R^(12b); and

[0246] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b); wherein said 5 to6 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, andtetrazolyl;

[0247] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy;

[0248] R¹³, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN, NR¹⁵R¹⁶,and CF₃;

[0249] R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;

[0250] R¹⁵, at each occurrence, is independently selected from H,methyl, ethyl, propyl, and butyl;

[0251] R¹⁶ at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C(═O)—,ethyl-C(═O)—, methyl-S(═O)₂—, ethyl-S(═O)₂—, and propyl-S(═O)₂—;

[0252] R¹⁸, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

[0253] R¹⁹, at each occurrence, is independently selected from H,methyl, and ethyl;

[0254] R²⁰ is H.

[0255] [5] In another more preferred embodiment the present inventionprovides a compound of Formula (I), wherein:

[0256] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0257] R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃,—CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂, —CH(OH)CH(CH₃)₂,—CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃, —CF₂CH₂CH(CH₃)₂,—CH(NHCH₃)CH₂CH(CH₃)₂, —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl-,cyclopentyl-, cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,1-NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,(4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,(3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,(3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,(2,4-diF-phenyl )CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,(2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,(3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,(2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,(2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,(3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,(3-F-5-Cl-phenyl)CH₂CH₂—, 4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—,phenyl-CH₂CH(OH)—, imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—;

[0258] Ring C is selected from:

[0259] Ring B is selected from:

[0260]  wherein each benzo fused ring is substituted with 0-1 R¹³;

[0261] W is a bond or —CH₂—;

[0262] X is a bond;

[0263] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or—N(CH₃)—,

[0264] Z is phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl,3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl,2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl,2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl,3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl,3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl,2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl, furanyl, thienyl, pyridyl,2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl,isoxazolyl, 1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, morpholino, N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,(3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—,(4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—,(4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—,4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—,(4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—,(2-Me-pyridyl)CH₂—, (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—,(1-imidazolyl)CH₂—, (oxazolyl)CH₂—, (isoxazolyl)CH₂—,(1-benzimidazolyl)CH₂—, (cyclopropyl)CH₂—, (cyclobutyl)CH₂—,(cyclopentyl)CH₂—, (cyclohexyl)CH₂—, (morpholino)CH₂—,(N-pipridinyl)CH₂—, phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—,(2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—,(2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,(2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,(3-Cl-4-F-phenyl)CH₂CH₂—, (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—,(4-MeO-phenyl)CH₂CH₂—, (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—,(4-Me-phenyl)CH₂CH₂—, (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—,(4-MeS-phenyl)CH₂CH₂—, (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,(4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—,(thienyl)CH₂CH₂—,(pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,(4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,(isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—,(cyclopropyl)CH₂CH₂—,(cyclobutyl)CH₂CH₂—,(cyclopentyl)CH₂CH₂—,(cyclohexyl)CH₂CH₂—,(morpholino)CH₂CH₂—, or (N-pipridinyl)CH₂CH₂—;

[0265] R¹⁰ is H, methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl,(4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—, 4-Cl-phenyl, (4-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,(4-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—, or(4-CF₃-phenyl)CH₂CH₂—;

[0266] R¹¹, at each occurrence, is independently selected from H, ═O,methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl, (4-F-phenyl)CH₂—,(4-F-phenyl)CH₂CH₂—, 3-F-phenyl, (3-F-phenyl)CH₂—, (3-F-phenyl)CH₂CH₂—,2-F-phenyl, (2-F-phenyl)CH₂—, (2-F-phenyl)CH₂CH₂—, 4-Cl-phenyl,(4-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂CH₂—, 3-Cl-phenyl, (3-Cl-phenyl)CH₂—,(3-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,(4-CH₃-phenyl)CH₂CH₂—, 3-CH₃-phenyl, (3-CH₃-phenyl)CH₂—,(3-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—,(4-CF₃-phenyl)CH₂CH₂—, cyclopentyl, pyrid-2-yl, pyrid-3-yl, andpyrid-4-yl;

[0267] R¹³, at each occurrence, is independently selected from H, F, Cl,OH, —CH₃, —CH₂CH₃, —OCH₃, and —CF₃; and

[0268] R²⁰ is H.

[0269] In another preferred embodiment the present invention provides acompound of Formula (I), wherein:

[0270] R³ is —(CR⁷R^(7a))_(n)—R⁴, —(CR⁷R^(7a))_(l)—S—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—O—(CR⁷R^(7a))_(m)—R⁴, or—(CR⁷R^(7a))_(l)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴;

[0271] n is 0, 1, or 2;

[0272] m is 0, 1, or 2;

[0273] l is 1 or 2;

[0274] Ring C is a 3 to 8 membered carbocycle substituted with 0-4 R²¹;optionally, the carbocycle contains a heteroatom selected from —O—, and—N(R²⁰)—;

[0275] R⁴ is H, OH, OR^(14a),

[0276] C₁-C₆ alkyl substituted with 0-3 R^(4a),

[0277] C₂-C₆ alkenyl substituted with 0-3 R^(4a),

[0278] C₂-C₆ alkynyl substituted with 0-3 R^(4a),

[0279] C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),

[0280] C₆-C₁₀ aryl substituted with 0-3 R^(4b), or

[0281] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(4b);

[0282] R^(4a), at each occurrence, is independently selected from is H,F, Cl, Br, I, CF₃,

[0283] C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),

[0284] C₆-C₁₀ aryl substituted with 0-3 R^(4b), or

[0285] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(4b);

[0286] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;

[0287] R⁶ is H, methyl, or ethyl;

[0288] R⁷, at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, CF₃, phenyl and C₁-C₄ alkyl;

[0289] R^(7a), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, CF₃, and C₁-C₄ alkyl;

[0290] R^(7b) is independently selected from H, methyl, ethyl, propyl,and butyl;

[0291] Ring B is a 7 membered lactam,

[0292] wherein the lactam is saturated, partially saturated orunsaturated;

[0293] wherein each additional lactam carbon is substituted with 0-2R¹¹; and,

[0294] optionally, the lactam contains a heteroatom selected from, —O—,—S—, —S(═O)—, —S(═O)₂—, —N═, —NH—, and —N(R¹⁰)—;

[0295] R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,S(═O)₂R¹⁷;

[0296] C₁-C₆ alkyl optionally substituted with 0-2 R^(10a);

[0297] C₆-C₁₀ aryl substituted with 0-4 R^(10b);

[0298] C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or

[0299] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(10b);

[0300] R^(10a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, phenylsubstituted with 0-4 R^(10b); or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(10b);

[0301] R^(10b), at each occurrence, is independently selected from H,OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, or CF₃;

[0302] R¹¹, at each occurrence, is independently selected from H, C₁-C₄alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;

[0303] C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);

[0304] C₆-C₁₀ aryl substituted with 0-3 R^(11b);

[0305] C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); or

[0306] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(11b);

[0307] R^(11a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenylsubstituted with 0-3 R^(11b);

[0308] R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄haloalkoxy;

[0309] additionally, two R¹¹ substituents on adjacent atoms may becombined to form a benzo fused radical; wherein said benzo fused radicalis substituted with 0-3 R¹³;

[0310] additionally, two R¹¹ substituents on adjacent atoms may becombined to form a 5 to 6 membered heteroaryl fused radical, whereinsaid 5 to 6 membered heteroaryl fused radical comprises 1 or 2heteroatoms selected from N, O, and S; wherein said 5 to 6 memberedheteroaryl fused radical is substituted with 0-3 R¹³;

[0311] additionally, two R¹¹ substituents on the same or adjacent carbonatoms may be combined to form a C₃-C₆ carbocycle substituted with 0-3R¹³;

[0312] W is (CR⁸R^(8a))_(p)—;

[0313] p is 0, 1, or 2;

[0314] R⁸ and R^(8a), at each occurrence, are independently selectedfrom H, F, C₁-C₃ alkyl, C₂-C₃ alkenyl, C₂-C₃ alkynyl and C₃-C₆cycloalkyl;

[0315] X is a bond;

[0316] C₆-C₁₀ aryl substituted with 0-3 R^(Xb);

[0317] C₃-C₁₀ carbocycle substituted with 0-2 R^(Xb); or

[0318] 5 to 10 membered heterocycle substituted with 0-2 R^(Xb);

[0319] R^(Xb), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;

[0320] Y is a bond or —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—;

[0321] t is 0, 1, or 2;

[0322] u is 0, 1, or 2;

[0323] R⁹ and R^(9a), at each occurrence, are independently selectedfrom H, F, C₁-C₄ alkyl or C₃-C₆ cycloalkyl;

[0324] V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,—C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂, —S(═O)₂NR^(19b)—,—NR^(19b)S(═O)—, or —S(═O)NR^(19b)—;

[0325] Z is H;

[0326] C₁-C₃ alkyl substituted with 1-2 R¹²;

[0327] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0328] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0329] 5 to 10 membered heterocycle substituted with 0-3 R^(12b);

[0330] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄haloalkoxy;

[0331] R¹³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

[0332] R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;

[0333] R^(14a) is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;

[0334] R¹⁵, at each occurrence, is independently selected from H, C₁-C₆alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0335] R¹⁶, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0336] R¹⁷ is H, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, aryl substituted by 0-4R^(17a), or —CH₂-aryl substituted by 0-4 R^(17a);

[0337] R^(17a) is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃, S(O)CH₃, SO₂CH₃,—NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl;

[0338] R¹⁸, at each occurrence, is independently selected from H, C₁-C₆alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—; and

[0339] R¹⁹, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₀-C₆alkyl)-S(═O)₂—

[0340] R²⁰ is H or C(═O)R¹⁷;

[0341] R²¹, at each occurrence, is independently selected from H, C₁-C₄alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;

[0342] C₁-C₆ alkyl optionally substituted with 0-3 R^(21a);

[0343] C₆-C₁₀ aryl substituted with 0-3 R^(21b);

[0344] C₃-C₁₀ carbocycle substituted with 0-3 R^(21b); or

[0345] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(21b);

[0346] R^(21a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃;

[0347] phenyl substituted with 0-3 R^(21b);

[0348] C₃-C₆ cycloalkyl substituted with 0-3 R^(21b); and

[0349] 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(21b);

[0350] R^(21b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0351] additionally, two R²¹ substituents on the same or adjacent carbonatoms may be combined to form a C₃-C₆ carbocycle substituted with 0-3R²³;

[0352] additionally, two R²¹ substituents on adjacent atoms may becombined to form a benzo fused radical; wherein said benzo fused radicalis substituted with 0-4 R²³; and

[0353] R²³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃.

[0354] [6] In another preferred embodiment the present inventionprovides a compound of Formula (I):

[0355] or a stereoisomer, pharmaceutically acceptable salt or prodrugthereof, wherein:

[0356] L is —NR²⁶C(═O)—, —C(═O)NR²⁶—, —NR²⁶C(═O)O—, —OC(═O)NR²⁶, or—NR²⁶C(═O)NR²⁶—;

[0357] R³ is —(CR⁷R^(7a))_(n)—R⁴, —(CR⁷R^(7a))_(l)—S—R⁴,—(CR⁷R^(7a))_(l)—O—R⁴; —(CR⁷R^(7a))_(l)—N(R^(7b))—R⁴,—(CR⁷R^(7a))_(l)—S(═O)—R⁴, or —(CR⁷R^(7a))_(l)—S(═O)₂—R⁴;

[0358] n is 0, 1 or 2;

[0359] l is 1 or 2;

[0360] R⁴ is H,

[0361] C₁-C₈ alkyl substituted with 0-3 R^(4a),

[0362] C₂-C₈ alkenyl substituted with 0-3 R^(4a),

[0363] C₂-C₈ alkynyl substituted with 0-3 R^(4a),

[0364] C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),

[0365] C₆-C₁₀ aryl substituted with 0-3 R^(4b), or

[0366] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(4b);

[0367] R^(4a), at each occurrence, is independently selected from H, OH,F, Cl, Br, I, NR¹⁵R¹⁶, CF₃,

[0368] C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),

[0369] C₆-C₁₀ aryl substituted with 0-3 R^(4b), and

[0370] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(4b);

[0371] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0372] Ring C is a 3-8 membered carbocycle;

[0373] wherein said 3-8 membered carbocycle is saturated or partiallyunsaturated;

[0374] wherein said 3-8 membered carbocycle is substituted with 0-4 R²¹;and

[0375] optionally, the carbocycle contains a heteroatom selected from—O— and —N(R²⁰)—;

[0376] additionally, two R²¹ substituents on adjacent atoms may becombined to form a benzo fused radical; wherein said benzo fused radicalis substituted with 0-4 R²³;

[0377] additionally, two R²¹ substituents on adjacent atoms may becombined to form a 5 to 6 membered heteroaryl fused radical, whereinsaid 5 to 6 membered heteroaryl fused radical comprises 1 or 2heteroatoms selected from N, O, and S; wherein said 5 to 6 memberedheteroaryl fused radical is substituted with 0-3 R²³;

[0378] additionally, two R²¹ substituents on the same or adjacent carbonatoms may be combined to form a C₃-C₆ carbocycle substituted with 0-3R²³;

[0379] R²¹, at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶,OR^(14a), C₁-C₄ alkyl, C₂-C₆ alkenyl, alkynyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—, C₃-C₆ carbocycle,phenyl, and a 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur;

[0380] R⁶ is H, methyl, or ethyl;

[0381] R⁷, at each occurrence, is independently H or C₁-C₄ alkyl;

[0382] R^(7a), at each occurrence, is independently H or C₁-C₄ alkyl;

[0383] R^(7b) is H or C₁-C₄ alkyl;

[0384] Ring B is selected from:

[0385] R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,S(═O)₂R¹⁷;

[0386] C₁-C₆ alkyl optionally substituted with 0-3 R^(10a);

[0387] C₆-C₁₀ aryl substituted with 0-4 R^(10b);

[0388] C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or

[0389] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(10b);

[0390] R^(10a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or arylsubstituted with 0-4 R^(10b);

[0391] R^(10b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0392] R¹¹, at each occurrence, is independently selected from H, C₁-C₄alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;

[0393] C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);

[0394] C₆-C₁₀ aryl substituted with 0-3 R^(11b);

[0395] C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); and

[0396] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(11b);

[0397] R^(11a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃;

[0398] phenyl substituted with 0-3 R^(11b);

[0399] C₃-C₆ cycloalkyl substituted with 0-3 R^(11b); and

[0400] 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(11b);

[0401] R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0402] W is a bond or —(CH₂)_(p)—;

[0403] p is 1 or 2;

[0404] X is a bond;

[0405] phenyl substituted with 0-2 R^(Xb);

[0406] C₃-C₆ carbocycle substituted with 0-2 R^(Xb); or

[0407] 5 to 6 membered heterocycle substituted with 0-2 R^(Xb);

[0408] R^(Xb), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, C₁-C₃ haloalkoxy, and C₁-C₃halothioalkoxy;

[0409] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,—C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S—(═O)₂—, —S(═O)₂NR^(19b)—,—NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—;

[0410] Z is H;

[0411] C₁-C₈ alkyl substituted with 0-3 R^(12a);

[0412] C₂-C₆ alkenyl substituted with 0-3 R^(12a);

[0413] C₂-C₆ alkynyl substituted with 0-3 R^(12a);

[0414] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0415] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0416] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0417] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃,

[0418] C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,

[0419] C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,

[0420] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0421] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and

[0422] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0423] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0424] R¹³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

[0425] R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, orC₃-C₆ cycloalkyl;

[0426] R^(14a) is H, phenyl, benzyl, or C₁-C₄ alkyl;

[0427] R¹⁵, at each occurrence, is independently selected from H, C₁-C₆alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0428] R¹⁶, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0429] R¹⁷ is H, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, aryl substituted by 0-4R^(17a), or —CH₂-aryl substituted by 0-4 R^(17a);

[0430] R^(17a) is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃, S(O)CH₃, SO₂CH₃,—NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl;

[0431] R¹⁸, at each occurrence, is independently selected from H, C₁-C₆alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0432] R¹⁹, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

[0433] R^(19b), at each occurrence, is independently is H or C₁-C₄alkyl;

[0434] R²⁰ is H, C₁-C₄ alkyl, or C(═O)OR¹⁷;

[0435] R²³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶ ₁, and CF₃;and

[0436] R²⁶ is H or C₁-C₄ alkyl.

[0437] [7] In another preferred embodiment the present inventionprovides a compound of Formula (Ia):

[0438] or a stereoisomer, pharmaceutically acceptable salt or prodrugthereof, wherein:

[0439] L is —NR²⁶C(═O)—, —C(═O)NR²⁶—, —NR²⁶C(═O)O—, —OC(═O)NR²⁶, or—NR²⁶C(═O) NR²⁶—;

[0440] R³ is —(CHR⁷)_(n)—R⁴, —(CHR⁷)_(l)—S—R⁴, —(CHR⁷)_(l)—O—R⁴;—(CR⁷R^(7a))_(l)—N(R^(7b))—R⁴, —(CR⁷R^(7a))_(l)—S(═O)—R⁴, or—(CR⁷R^(7a))_(l)—S(═O)₂—R⁴;

[0441] n is 0, 1 or 2;

[0442] l is 1 or 2;

[0443] R⁴ is H,

[0444] C₁-C₈ alkyl substituted with 0-3 R^(4a),

[0445] C₂-C₈ alkenyl substituted with 0-3 R^(4a),

[0446] C₂-C₈ alkynyl substituted with 0-3 R^(4a),

[0447] C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),

[0448] C₆-C₁₀ aryl substituted with 0-3 R^(4b), or

[0449] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(4b);

[0450] R^(4a), at each occurrence, is independently selected from H, OH,F, Cl, Br, I, NR¹⁵R¹⁶ CF₃,

[0451] C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),

[0452] C₆-C₁₀ aryl substituted with 0-3 R^(4b), and

[0453] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(4b);

[0454] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0455] Ring C is a 3-8 membered carbocycle;

[0456] wherein said 3-8 membered carbocycle is saturated or partiallyunsaturated;

[0457] wherein said 3-8 membered carbocycle is substituted with 0-4 R²¹;

[0458] optionally, the carbocycle contains a heteroatom selected from—O—, and —N(R²⁰)—;

[0459] additionally, two R²¹ substituents on adjacent atoms may becombined to form a benzo fused radical; wherein said benzo fused radicalis substituted with 0-4 R²³;

[0460] additionally, two R²¹ substituents on the same or adjacent carbonatoms may be combined to form a C₃-C₆ carbocycle substituted with 0-3R²³;

[0461] R²¹, at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶OR^(14a), C₁-C₄ alkyl, C₂-C₆ alkenyl, alkynyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl,

[0462] C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—,

[0463] C₃-C₆ carbocycle, phenyl, and a

[0464] 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur;

[0465] R⁷, at each occurrence, is independently H, methyl, or ethyl;

[0466] R^(7b) is H, methyl, or ethyl;

[0467] Ring B is selected from:

[0468] R¹¹, at each occurrence, is independently selected from H, C₁-C₄alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;

[0469] C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);

[0470] C₆-C₁₀ aryl substituted with 0-3 R^(11b);

[0471] C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); and

[0472] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(11b);

[0473] R^(11a), at each occurrence, is independently selected from H,C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃;

[0474] phenyl substituted with 0-3 R^(11b);

[0475] C₃-C₆ cycloalkyl substituted with 0-3 R^(11b); and

[0476] 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(11b);

[0477] R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0478] W is a bond or —(CH₂)_(p)—;

[0479] p is 1 or 2;

[0480] X is a bond; phenyl substituted with 0-2 R^(Xb); C₃-C₆ carbocyclesubstituted with 0-2 R^(Xb); or 5 to 6 membered heterocycle substitutedwith 0-2 R^(Xb);

[0481] R^(Xb), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, C₁-C₃ haloalkoxy, and C₁-C₃halothioalkoxy;

[0482] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,—C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—,—NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—;

[0483] Z is H;

[0484] C₁-C₈ alkyl substituted with 0-3 R^(12a);

[0485] C₂-C₆ alkenyl substituted with 0-3 R^(12a);

[0486] C₂-C₆ alkynyl substituted with 0-3 R^(12a);

[0487] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0488] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0489] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0490] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃,

[0491] C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,

[0492] C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,

[0493] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0494] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and

[0495] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0496] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0497] R¹³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

[0498] R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, orC₃-C₆ cycloalkyl;

[0499] R^(14a) is H, phenyl, benzyl, or C₁-C₄ alkyl;

[0500] R¹⁵, at each occurrence, is independently selected from H, C₁-C₆alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0501] R¹⁶, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0502] R¹⁷ is H, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, aryl substituted by 0-4R^(17a), or —CH₂-aryl substituted by 0-4 R^(17a);

[0503] R^(17a) is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃, S(O)CH₃, SO₂CH₃,—NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl;

[0504] R¹⁸, at each occurrence, is independently selected from H, C₁-C₆alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C (═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0505] R¹⁹, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl;

[0506] R²⁰ is H, C₁-C₄ alkyl, or C(═O)OR¹⁷;

[0507] R²³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; and

[0508] R²⁶ is H or C₁-C₄ alkyl.

[0509] [8] In another preferred embodiment the present inventionprovides a compound of Formula (Ic):

[0510] or a stereoisomer, pharmaceutically acceptable salt or prodrugthereof, wherein:

[0511] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0512] R³ is —(CH₂)_(n)—R⁴, —(CH₂)_(l)—S—R⁴, —(CH₂)_(l)—O—R⁴, or—(CH₂)_(l)—N(R^(7b))—R⁴;

[0513] n is 0, 1 or 2;

[0514] l is 1 or 2;

[0515] R⁴ is C₁-C₈ alkyl substituted with 0-3 R^(4a), C₂-C₈ alkenylsubstituted with 0-3 R^(4a), C₂-C₈ alkynyl substituted with 0-3 R^(4a),C₃-C₁₀ carbocycle substituted with 0-3 R^(4b), C₆-C₁₀ aryl substitutedwith 0-3 R^(4b), or 5 to 10 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 10 membered heterocycle is substituted with 0-3 R^(4b);

[0516] R^(4a), at each occurrence, is independently selected from H, OH,F, Cl, Br, I, NR¹⁵R¹⁶, CF₃,

[0517] C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),

[0518] C₆-C₁₀ aryl substituted with 0-3 R^(4b), and

[0519] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(4b);

[0520] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0521] R^(7b) is H, methyl, or ethyl;

[0522] Ring C is a 3-8 membered carbocycle;

[0523] wherein said 3-8 membered carbocycle is saturated or partiallyunsaturated;

[0524] wherein said 3-8 membered carbocycle is substituted with 0-3 R²¹;

[0525] optionally, the carbocycle contains a heteroatom selected from—O—, and —N(R²⁰)—;

[0526] R²¹, at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶,OR^(14a), C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

[0527] W is a bond, —CH₂—, —CH₂CH₂—;

[0528] X is a bond; phenyl substituted with 0-2 R^(Xb); C₃-C₆ cycloalkylsubstituted with 0-2 R^(Xb); or 5 to 6 membered heterocycle substitutedwith 0-2 R^(Xb);

[0529] R^(Xb), at each occurrence, is independently selected from H, OH,Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

[0530] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,—C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—,—NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—;

[0531] Z is H;

[0532] C₁-C₈ alkyl substituted with 0-3 R^(12a);

[0533] C₂-C₆ alkenyl substituted with 0-3 R^(12a);

[0534] C₂-C₆ alkynyl substituted with 0-3 R¹²a;

[0535] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0536] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0537] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0538] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃,

[0539] C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,

[0540] C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,

[0541] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0542] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and

[0543] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0544] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0545] R¹³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

[0546] R¹⁴ a is H, phenyl, benzyl, or C₁-C₄ alkyl;

[0547] R¹⁵, at each occurrence, is independently selected from H, C₁-C₆alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄alkyl)-S(═O)₂—;

[0548] R¹⁶, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄alkyl)-S(═O)₂—; and

[0549] R²⁰ is H or C₁-C₄ alkyl.

[0550] [9] In another preferred embodiment the present inventionprovides a compound of Formula (Ic) wherein:

[0551] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0552] R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

[0553] R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenylsubstituted with 0-3 R^(4a), C₂-C₆ alkynyl substituted with 0-3 R^(4a),C₃-C₆ carbocycle substituted with 0-3 R^(4b), phenyl substituted with0-3 R^(4b), or 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b);

[0554] R^(4a), at each occurrence, is independently selected from H, OH,F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆ carbocycle substituted with 0-3R^(4b), phenyl substituted with 0-3 R^(4b), and 5 to 6 memberedheterocycle containing 1 to 3 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 6 membered heterocycle issubstituted with 0-3 R^(4b);

[0555] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0556] Ring C is a 3-6 membered carbocycle;

[0557] wherein said 3-6 membered carbocycle is saturated or partiallyunsaturated;

[0558] wherein said 3-6 membered carbocycle is substituted with 0-2 R²¹;

[0559] optionally, the carbocycle contains a heteroatom selected from—O—, and —N(R²⁰)—;

[0560] R²¹, at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, methyl, ethyl, methoxy,ethoxy, allyl, —OCF₃, and —SCF₃;

[0561] W is a bond, —CH₂—, —CH₂CH₂—;

[0562] X is a bond;

[0563] phenyl substituted with 0-1 R^(Xb);

[0564] C₃-C₆ cycloalkyl substituted with 0-1 R^(Xb); or 5 to 6 memberedheterocycle substituted with 0-1 R^(Xb); R^(Xb) is selected from H, OH,Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl,propyl, methoxy, ethoxy, propoxy, and —OCF₃;

[0565] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—,—N(CH₃)—, or —N(CH₂CH₃)—;

[0566] Z is H;

[0567] C₁-C₈ alkyl substituted with 0-3 R^(12a);

[0568] C₂-C₆ alkenyl substituted with 0-3 R^(12a);

[0569] C₂-C₆ alkynyl substituted with 0-3 Ri²a;

[0570] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0571] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0572] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0573] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄haloalkoxy, C₁-C₄ haloalkyl-S—, C₆-C₁₀ aryl substituted with 0-4R^(12b); C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and 5 to 10membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycleis substituted with 0-3 R^(12b);

[0574] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0575] R¹³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

[0576] R¹⁵, at each occurrence, is independently selected from H, C₁-C₄alkyl, and benzyl;

[0577] R¹⁶, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C(═O)—,ethyl-C(═O)—, methyl-S(═O)₂—, ethyl-S(═O)₂—, and propyl-S(═O)₂—; and

[0578] R²⁰ is H or C₁-C₄ alkyl.

[0579] [10] In another preferred embodiment the present inventionprovides a compound of Formula (Ic) wherein:

[0580] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0581] R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

[0582] R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenylsubstituted with 0-3 R^(4a), or C₂-C₆ alkynyl substituted with 0-3R^(4a);

[0583] R^(4a), at each occurrence, is independently selected from is H,OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆ carbocycle substituted with 0-3R^(4b), phenyl substituted with 0-3 R^(4b), and 5 to 6 memberedheterocycle containing 1 to 3 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 6 membered heterocycle issubstituted with 0-3 R^(4b); wherein said 5 to 6 membered heterocycle isselected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl,thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl,oxazolyl, isoxazolyl, and tetrazolyl;

[0584] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0585] Ring C is a 3-6 membered carbocycle selected from:

[0586]  wherein said 3-6 membered carbocycle is substituted with 0-1R²¹;

[0587] R²¹ is selected from H, OH, Cl, F, CN, CF₃, methyl, ethyl,methoxy, ethoxy, allyl, and —OCF₃;

[0588] W is a bond or —CH₂—;

[0589] X is a bond, phenyl, C₃-C₆ cycloalkyl or 5 to 6 memberedheterocycle;

[0590] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—,—N(CH₃)—, or —N(CH₂CH₃)—;

[0591] Z is H;

[0592] C₁-C₈ alkyl substituted with 0-3 R^(12a);

[0593] C₂-C₆ alkenyl substituted with 0-3 R^(12a);

[0594] C₂-C₆ alkynyl substituted with 0-3 R^(12a);

[0595] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0596] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0597] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0598] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy;

[0599] phenyl substituted with 0-4 R^(12b);

[0600] C₃-6 carbocycle substituted with 0-4 R^(12b); and

[0601] 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(12b);

[0602] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy;

[0603] R¹³, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN, NR¹⁵R¹⁶,and CF₃;

[0604] R¹⁵, at each occurrence, is independently selected from H,methyl, ethyl, propyl, and butyl; and

[0605] R¹⁶, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, benzyl, and phenethyl; and

[0606] R²⁰ is H, methyl, or ethyl.

[0607] [11] In another preferred embodiment the present inventionprovides a compound of Formula (Ic) wherein:

[0608] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0609] Ring C is selected from:

[0610] R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃,—CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂, —CH(OH)CH(CH₃)₂,—CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃, —CF₂CH₂CH(CH₃)₂, —CH(NHCH₃)CH₂CH(CH₃)₂, —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl-,cyclopentyl-, cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,1-NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,(4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,(3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,(3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂ —, (2,3-diF-phenyl)CH₂CH₂—,(2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—, phenyl-CH₂CH(OH)—,imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—;

[0611] W is a bond or —CH₂—;

[0612] X is a bond;

[0613] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or—N(CH₃)—,

[0614] Z is methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl,s-butyl, t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl,2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl,2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl,2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl,3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl,3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl,2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl, furanyl, thienyl, pyridyl,2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl,isoxazolyl, 1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, morpholino, N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,(3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—,(4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—,(4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—,4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—,(4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—,(2-Me-pyridyl)CH₂—, (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—,(1-imidazolyl)CH₂—, (oxazolyl)CH₂—, (isoxazolyl)CH₂—,(1-benzimidazolyl)CH₂—, (cyclopropyl)CH₂—, (cyclobutyl)CH₂—,(cyclopentyl)CH₂—, (cyclohexyl)CH₂—, (morpholino)CH₂—,(N-pipridinyl)CH₂—, phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—,(2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—,(2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,(2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,(3-Cl-4-F-phenyl)CH₂CH₂—, (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—,(4-MeO-phenyl)CH₂CH₂—, (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—,(4-Me-phenyl)CH₂CH₂—, (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—,(4-MeS-phenyl)CH₂CH₂—, (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,(4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—,(thienyl)CH₂CH₂—,(pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,(4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,(isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—,(cyclopropyl)CH₂CH₂—,(cyclobutyl)CH₂CH₂—,(cyclopentyl)CH₂CH₂—,(cyclohexyl)CH₂CH₂—,(morpholino)CH₂CH₂—, or (N-pipridinyl)CH₂CH₂—;

[0615] R¹³, at each occurrence, is independently selected from H, F, Cl,OH, —CH₃, —CH₂CH₃, —OCH₃, or —CF₃.

[0616] R²⁰ is H, methyl, or ethyl.

[0617] [12] In another preferred embodiment the present inventionprovides a compound of Formula (Id) and (Ie)

[0618] or a stereoisomer, pharmaceutically acceptable salt or prodrugthereof, wherein:

[0619] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0620] R³ is —(CH₂)_(n)—R⁴, —(CH₂)_(l)—S—R⁴, —(CH₂)_(l)—O—R⁴, or—(CH₂)_(l)-N(R^(7b))—R⁴;

[0621] n is 0, 1 or 2;

[0622] l is 1 or 2;

[0623] R⁴ is C₁-C₈ alkyl substituted with 0-3 R^(4a), C₂-C₈ alkenylsubstituted with 0-3 R^(4a), C₂-C₈ alkynyl substituted with 0-3 R^(4a),C₃-C₁₀ carbocycle substituted with 0-3 R^(4b), C₆-C₁₀ aryl substitutedwith 0-3 R^(4b), or 5 to 10 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 10 membered heterocycle is substituted with 0-3 R^(4b);

[0624] R^(4a), at each occurrence, is independently selected from H, OH,F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₁₀ carbocycle substituted with 0-3R^(4b), C₆-C₁₀ aryl substituted with 0-3 R^(4b), and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(4b);

[0625] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0626] R^(7b) is H, methyl, or ethyl;

[0627] Ring C is a 3-8 membered carbocycle;

[0628] wherein said 3-8 membered carbocyclic moiety is saturated orpartially saturated;

[0629] wherein said 3-8 membered carbocyclic moiety is substituted with0-3 R²¹;

[0630] optionally, the carbocycle contains a heteroatom selected from—O— and —N(R²⁰)—;

[0631] R²¹, at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶,OR^(14a), C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

[0632] R¹¹, at each occurrence, is independently selected from H, ═O,NR¹⁸R¹⁹, CF₃;

[0633] C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);

[0634] phenyl substituted with 0-3 R^(11b);

[0635] C₃-C₆ carbocycle substituted with 0-3 R^(11b); and

[0636] 5 to 7 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 7membered heterocycle is substituted with 0-3 R^(11b); wherein said 5 to7 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,homopiperidinyl, and tetrazolyl;

[0637] R^(11a), at each occurrence, is independently selected from H,C₁-C₄ alkyl, OR¹⁴, F, Cl, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with0-3 R^(11b);

[0638] R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

[0639] W is a bond, —CH₂—, —CH₂CH₂—;

[0640] X is a bond;

[0641] phenyl substituted with 0-2 R^(Xb);

[0642] C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or

[0643] 5 to 6 membered heterocycle substituted with 0-2 R^(Xb);

[0644] R^(Xb), at each occurrence, is independently selected from H, OH,Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

[0645] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,—C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—,—NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—;

[0646] Z is H;

[0647] C₁-C₈ alkyl substituted with 0-3 R^(12a);

[0648] C₂-C₆ alkenyl substituted with 0-3 R^(12a);

[0649] C₂-C₆ alkynyl substituted with 0-3 R^(12a);

[0650] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0651] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0652] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0653] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃,

[0654] C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,

[0655] C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,

[0656] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0657] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and

[0658] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0659] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl- S—;

[0660] R¹³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

[0661] R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, orC₃-C₆ cycloalkyl;

[0662] R^(14a) is H, phenyl, benzyl, or C₁-C₄ alkyl;

[0663] R¹⁵, at each occurrence, is independently selected from H, C₁-C₆alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0664] R¹⁶, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄alkyl)-S(═O)₂—;

[0665] R¹⁸ at each occurrence, is independently selected from H, C₁-C₆alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0666] R¹⁹, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl; and

[0667] R²⁰ is H or C₁-C₄ alkyl.

[0668] [13] In another preferred embodiment the present inventionprovides a compound of Formula (Id) and (Ie) wherein:

[0669] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0670] R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

[0671] R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenylsubstituted with 0-3 R^(4a), C₂-C₆ alkynyl substituted with 0-3 R^(4a),C₃-C₆ carbocycle substituted with 0-3 R^(4b), phenyl substituted with0-3 R^(4b), or 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b);

[0672] R^(4a), at each occurrence, is independently selected from is H,OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆ carbocycle substituted with 0-3R^(4b), phenyl substituted with 0-3 R^(4b), or 5 to 6 memberedheterocycle containing 1 to 3 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 6 membered heterocycle issubstituted with 0-3 R^(4b);

[0673] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0674] Ring C is a 3-6 membered carbocycle;

[0675] wherein said 3-6 membered carbocyclic moiety is saturated orpartially unsaturated;

[0676] wherein said 3-6 membered carbocyclic moiety is substituted with0-2 R²¹;

[0677] optionally, the carbocycle contains a heteroatom selected from—O— and —N(R²⁰)—;

[0678] R²¹, at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, methyl, ethyl, methoxy,ethoxy, allyl, —OCF₃, and —SCF₃;

[0679] R¹¹, at each occurrence, is independently selected from H, ═O,NR¹⁸R¹⁹, CF₃;

[0680] C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);

[0681] phenyl substituted with 0-3 R^(11b);

[0682] C₃-C₆ carbocycle substituted with 0-3 R^(11b); and

[0683] 5 to 7 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 7membered heterocycle is substituted with 0-3 R^(11b); wherein said 5 to7 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,homopiperidinyl, and tetrazolyl;

[0684] R^(11a), at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, phenoxy, F, Cl,═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b);

[0685] R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

[0686] W is a bond, —CH₂—, —CH₂CH₂—;

[0687] X is a bond;

[0688] phenyl substituted with 0-1 R^(Xb);

[0689] C₃-C₆ cycloalkyl substituted with 0-1 R^(Xb); or

[0690] 5 to 6 membered heterocycle substituted with 0-1 R^(Xb);

[0691] R^(Xb) is selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, methoxy, ethoxy, propoxy,and —OCF₃;

[0692] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S (═O)₂—, —NH—,—N(CH₃)—, or —N(CH₂CH₃)—;

[0693] Z is H;

[0694] C₁-C₈ alkyl substituted with 0-3 R^(12a);

[0695] C₂-C₆ alkenyl substituted with 0-3 R^(12a);

[0696] C₂-C₆ alkynyl substituted with 0-3 R^(12a);

[0697] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0698] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0699] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0700] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃,

[0701] C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,

[0702] C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,

[0703] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0704] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0705] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0706] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0707] R¹³, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

[0708] R¹⁴ is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl;

[0709] R¹⁵, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, benzyl, and phenethyl;

[0710] R¹⁶, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C(═O)—,ethyl-C(═O)—, methyl-S(═O)₂—, and ethyl-S(═O)₂—;

[0711] R¹⁸, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

[0712] R¹⁹, at each occurrence, is independently selected from H,methyl, ethyl, propyl, and butyl;

[0713] R²⁰ is H or C₁-C₄ alkyl.

[0714] [14] In another preferred embodiment the present inventionprovides a compound of Formula (Id) and (Ie) wherein:

[0715] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0716] R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

[0717] R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenylsubstituted with 0-3 R^(4a), or C₂-C₆ alkynyl substituted with 0-3R^(4a);

[0718] R^(4a), at each occurrence, is independently selected from is H,OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃,

[0719] C₃-C₆ carbocycle substituted with 0-3 R^(4b),

[0720] phenyl substituted with 0-3 R^(4b), or

[0721] 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b); wherein said 5 to 6membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl,furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl,pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;

[0722] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0723] Ring C is a 3-6 membered carbocycle selected from:

[0724]  wherein said 3-6 membered carbocycle is substituted with 0-1R²¹;

[0725] R²¹ is selected from H, OH, Cl, F, CN, CF₃, methyl, ethyl,methoxy, ethoxy, allyl, and —OCF₃;

[0726] R¹¹, at each occurrence, is independently selected from H, ═O,NR¹⁸R¹⁹;

[0727] C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);

[0728] phenyl substituted with 0-3 R^(11b);

[0729] 5 to 7 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 7membered heterocycle is substituted with 0-3 R^(11b); wherein said 5 to7 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,homopiperidinyl, and tetrazolyl;

[0730] R^(11a), at each occurrence, is independently selected from H,methyl, ethyl, propyl, methoxy, ethoxy, propoxy, phenoxy, F, Cl, ═O,NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b);

[0731] R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

[0732] W is a bond or —CH₂—;

[0733] X is a bond, phenyl, C₃-C₆ cycloalkyl or 5 to 6 memberedheterocycle;

[0734] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—,—N(CH₃)—, or —N(CH₂CH₃)—;

[0735] Z is H;

[0736] C₁-C₈ alkyl substituted with 0-3 R^(12a);

[0737] C₂-C₆ alkenyl substituted with 0-3 R^(12a);

[0738] C₂-C₆ alkynyl substituted with 0-3 R^(12a);

[0739] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0740] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0741] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0742] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy;

[0743] phenyl substituted with 0-4 R^(12b);

[0744] C₃-6 carbocycle substituted with 0-4 R^(12b); or

[0745] 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(12b);

[0746] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy;

[0747] R¹³, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN, NR¹⁵R¹⁶,and CF₃;

[0748] R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;

[0749] R¹⁵, at each occurrence, is independently selected from H,methyl, ethyl, propyl, and butyl; and

[0750] R¹⁶, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, benzyl, and phenethyl.

[0751] R¹⁸, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

[0752] R¹⁹, at each occurrence, is independently selected from H,methyl, ethyl, propyl, and butyl; and

[0753] R²⁰ is H, methyl, or ethyl.

[0754] [15] In another preferred embodiment the present inventionprovides a compound of Formula (Id) and (Ie) wherein:

[0755] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0756] Ring C is selected from:

[0757] R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃,—CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂, —CH(OH)CH(CH₃)₂,—CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃, —CF₂CH₂CH(CH₃)₂,—CH(NHCH₃)CH₂CH(CH₃)₂, —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl-,cyclopentyl-, cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,1-NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,(4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,(3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,(3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,(2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,(2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,(3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,(2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,(2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,(3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,(3-F-5-Cl-phenyl)CH₂CH₂—, 4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—,phenyl-CH₂CH(OH)—, imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—;

[0758] W is a bond or —CH₂—;

[0759] X is a bond;

[0760] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or—N(CH₃)—,

[0761] Z is methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl,s-butyl, t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl,2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl,2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl,2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl,3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl,3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl,2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl, furanyl, thienyl, pyridyl,2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl,isoxazolyl, 1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, morpholino, N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,(3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—, (3-Meo-phenyl)CH₂—,(4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—,(4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—,4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—,(4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—,(2-Me-pyridyl)CH₂—, (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—,(1-imidazolyl)CH₂—, (oxazolyl)CH₂—, (isoxazolyl)CH₂—,(1-benzimidazolyl)CH₂—, (cyclopropyl)CH₂—, (cyclobutyl)CH₂—,(cyclopentyl)CH₂—, (cyclohexyl)CH₂—, (morpholino)CH₂—,(N-pipridinyl)CH₂—, phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—,(2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—,(2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,(2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,(3-Cl-4-F-phenyl)CH₂CH₂—, (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—,(4-MeO-phenyl)CH₂CH₂—, (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—,(4-Me-phenyl)CH₂CH₂—, (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—,(4-MeS-phenyl)CH₂CH₂—, (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,(4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—,(thienyl)CH₂CH₂—,(pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,(4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,(isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—,(cyclopropyl)CH₂CH₂—,(cyclobutyl)CH₂CH₂—,(cyclopentyl)CH₂CH₂—,(cyclohexyl)CH₂CH₂—,(morpholino)CH₂CH₂—, or (N-pipridinyl)CH₂CH₂—;

[0762] R¹¹, at each occurrence, is independently selected from H, ═O,methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl, (4-F-phenyl)CH₂—,(4-F-phenyl)CH₂CH₂—, 3-F-phenyl, (3-F-phenyl)CH₂—, (3-F-phenyl)CH₂CH₂—,2-F-phenyl, (2-F-phenyl)CH₂—, (2-F-phenyl)CH₂CH₂—, 4-Cl-phenyl,(4-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂CH₂—, 3-Cl-phenyl, (3-Cl-phenyl)CH₂—,(3-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,(4-CH₃-phenyl)CH₂CH₂—, 3-CH₃-phenyl, (3-CH₃-phenyl)CH₂—,(3-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—,(4-CF₃-phenyl)CH₂CH₂—, cyclopentyl, pyrid-2-yl, pyrid-3-yl, orpyrid-4-yl; and

[0763] R¹³, at each occurrence, is independently selected from H, F, Cl,OH, —CH₃, —CH₂CH₃, —OCH₃, or —CF₃.

[0764] [16] In another preferred embodiment the present inventionprovides a compound of Formula (If):

[0765] or a stereoisomer, pharmaceutically acceptable salt or prodrugthereof, wherein:

[0766] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0767] R³ is —(CH₂)_(n)—R⁴, —(CH₂)_(l)—S—R⁴, —(CH₂)_(l)—O—R⁴, or—(CH₂)_(l)—N(R^(7b))—R⁴;

[0768] n is 0, 1 or 2;

[0769] l is 1 or 2;

[0770] R⁴ is C₁-C₈ alkyl substituted with 0-3 R^(4a), C₂-C₈ alkenylsubstituted with 0-3 R^(4a), C₂-C₈ alkynyl substituted with 0-3 R^(4a),C₃-C₁₀ carbocycle substituted with 0-3 R^(4b), C₆-C₁₀ aryl substitutedwith 0-3 R^(4b), or 5 to 10 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 10 membered heterocycle is substituted with 0-3 R^(4b);

[0771] R^(4a), at each occurrence, is independently selected from H, OH,F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₁₀ carbocycle substituted with 0-3R^(4b), C₆-C₁₀ aryl substituted with 0-3 R^(4b), and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(4b);

[0772] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0773] R^(7b) is H, methyl, or ethyl;

[0774] Ring C is a 3-8 membered carbocycle;

[0775] wherein said 3-8 membered carbocyclic moiety is saturated orpartially saturated;

[0776] wherein said 3-8 membered carbocyclic moiety is substituted with0-3 R²¹;

[0777] optionally, the carbocycle contains a heteroatom selected from—O— and —N(R²⁰)—;

[0778] R²¹, at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶,OR^(14a), C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

[0779] R¹¹ is selected from H, ═O, NR¹⁸R¹⁹, CF₃;

[0780] C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);

[0781] phenyl substituted with 0-3 R^(11b);

[0782] C₃-C₆ carbocycle substituted with 0-3 R^(11b); and

[0783] 5 to 7 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 7membered heterocycle is substituted with 0-3 R^(11b); wherein said 5 to7 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,homopiperidinyl, and tetrazolyl;

[0784] R^(11a), at each occurrence, is independently selected from H,C₁-C₄ alkyl, OR¹⁴, F, Cl, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with0-3 R^(11b);

[0785] R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

[0786] W is a bond, —CH₂—, —CH₂CH₂—;

[0787] X is a bond;

[0788] phenyl substituted with 0-2 R^(Xb);

[0789] C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or

[0790] 5 to 6 membered heterocycle substituted with 0-2 R^(Xb);

[0791] R^(Xb), at each occurrence, is independently selected from H, OH,Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

[0792] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,—C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—,—NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—;

[0793] Z is H;

[0794] C₁-C₈ alkyl substituted with 0-3 R^(12a);

[0795] C₂-C₆ alkenyl substituted with 0-3 R^(12a);

[0796] C₂-C₆ alkynyl substituted with 0-3 R^(12a);

[0797] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0798] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0799] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0800] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃,

[0801] C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,

[0802] C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,

[0803] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0804] C₃-C₁O carbocycle substituted with 0-4 R^(12b); and

[0805] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0806] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0807] R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, orC₃-C₆ cycloalkyl;

[0808] R^(14a) is H, phenyl, benzyl, or C₁-C₄ alkyl;

[0809] R¹⁵, at each occurrence, is independently selected from H, C₁-C₆alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0810] R¹⁶, at each occurrence, is independently selected from H, OH,C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄alkyl)-S(═O)₂—;

[0811] R¹⁸, at each occurrence, is independently selected from H, C₁-C₆alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—;

[0812] R¹⁹, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl; and

[0813] R²⁰ is H or C₁-C₄ alkyl.

[0814] [17] In another preferred embodiment the present inventionprovides a compound of Formula (If) wherein:

[0815] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0816] R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

[0817] R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenylsubstituted with 0-3 R^(4a), C₂-C₆ alkynyl substituted with 0-3 R^(4a),C₃-C₆ carbocycle substituted with 0-3 R^(4b), phenyl substituted with0-3 R^(4b), or 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b);

[0818] R^(4a), at each occurrence, is independently selected from is H,OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆ carbocycle substituted with 0-3R^(4b), phenyl substituted with 0-3 R^(4b), or 5 to 6 memberedheterocycle containing 1 to 3 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 6 membered heterocycle issubstituted with 0-3 R^(4b);

[0819] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0820] Ring C is a 3-6 membered carbocycle;

[0821] wherein said 3-6 membered carbocyclic moiety is saturated orpartially unsaturated;

[0822] wherein said 3-6 membered carbocyclic moiety is substituted with0-2 R²¹;

[0823] optionally, the carbocycle contains a heteroatom selected from—O— and —N(R²⁰)—;

[0824] R²¹, at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, methyl, ethyl, methoxy,ethoxy, allyl, —OCF₃, and —SCF₃;

[0825] R¹¹ is selected from H, ═O, NR¹⁸R¹⁹, CF₃;

[0826] C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);

[0827] phenyl substituted with 0-3 R^(11b);

[0828] C₃-C₆ carbocycle substituted with 0-3 R^(11b); and

[0829] 5 to 7 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 7membered heterocycle is substituted with 0-3 R^(11b); wherein said 5 to7 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,homopiperidinyl, and tetrazolyl;

[0830] R^(11a), at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, phenoxy, F, Cl,═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b);

[0831] R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

[0832] W is a bond, —CH₂—, —CH₂CH₂—;

[0833] X is a bond;

[0834] phenyl substituted with 0-1 R^(Xb);

[0835] C₃-C₆ cycloalkyl substituted with 0-1 R^(Xb); or

[0836] 5 to 6 membered heterocycle substituted with 0-1 R^(Xb);

[0837] R^(Xb) is selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, methoxy, ethoxy, propoxy,and —OCF₃;

[0838] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—,—N(CH₃)—, or —N(CH₂CH₃)—;

[0839] Z is H;

[0840] C₁-C₈ alkyl substituted with 0-3 R^(12a);

[0841] C₂-C₆ alkenyl substituted with 0-3 R^(12a);

[0842] C₂-C₆ alkynyl substituted with 0-3 R^(12a);

[0843] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0844] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0845] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0846] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃,

[0847] C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,

[0848] C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,

[0849] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0850] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0851] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0852] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—;

[0853] R¹⁴ is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl;

[0854] R¹⁵, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, benzyl, and phenethyl;

[0855] R¹⁶, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C(═O)—,ethyl-C(═O)—, methyl-S(═O)₂—, and ethyl-S(═O)₂—;

[0856] R¹⁸, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

[0857] R¹⁹, at each occurrence, is independently selected from H,methyl, ethyl, propyl, and butyl;

[0858] R²⁰ is H or C₁-C₄ alkyl.

[0859] [18] In another preferred embodiment the present inventionprovides a compound of Formula (If) wherein:

[0860] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0861] R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

[0862] R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenylsubstituted with 0-3 R^(4a), or C₂-C₆ alkynyl substituted with 0-3R^(4a);

[0863] R^(4a), at each occurrence, is independently selected from is H,OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆ carbocycle substituted with 0-3R^(4b), phenyl substituted with 0-3 R^(4b), or 5 to 6 memberedheterocycle containing 1 to 3 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 6 membered heterocycle issubstituted with 0-3 R^(4b); wherein said 5 to 6 membered heterocycle isselected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl,thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl,oxazolyl, isoxazolyl, and tetrazolyl;

[0864] R^(4b), at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—;

[0865] Ring C is a 3-6 membered carbocycle selected from:

[0866]  wherein said 3-6 membered carbocycle is substituted with 0-1R²¹;

[0867] R²¹ is selected from H, OH, Cl, F, CN, CF₃, methyl, ethyl,methoxy, ethoxy, allyl, and —OCF₃;

[0868] R¹¹ is selected from H, ═O, NR¹⁸R¹⁹;

[0869] C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);

[0870] phenyl substituted with 0-3 R^(11b);

[0871] 5 to 7 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 7membered heterocycle is substituted with 0-3 R^(11b); wherein said 5 to7 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,homopiperidinyl, and tetrazolyl;

[0872] R^(11a), at each occurrence, is independently selected from H,methyl, ethyl, propyl, methoxy, ethoxy, propoxy, phenoxy, F, Cl, ═O,NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b);

[0873] R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

[0874] W is a bond or —CH₂—;

[0875] X is a bond, phenyl, C₃-C₆ cycloalkyl or 5 to 6 memberedheterocycle;

[0876] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—,—N(CH₃)—, or —N(CH₂CH₃)—;

[0877] Z is H;

[0878] C₁-C₈ alkyl substituted with 0-3 R^(12a);

[0879] C₂-C₆ alkenyl substituted with 0-3 R^(12a);

[0880] C₂-C₆ alkynyl substituted with 0-3 R^(12a);

[0881] C₆-C₁₀ aryl substituted with 0-4 R^(12b);

[0882] C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or

[0883] 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b);

[0884] R^(12a), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy;

[0885] phenyl substituted with 0-4 R^(12b);

[0886] C₃-6 carbocycle substituted with 0-4 R^(12b); or

[0887] 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(12b);

[0888] R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy;

[0889] R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;

[0890] R¹⁵, at each occurrence, is independently selected from H,methyl, ethyl, propyl, and butyl; and

[0891] R¹⁶, at each occurrence, is independently selected from H, OH,methyl, ethyl, propyl, butyl, benzyl, and phenethyl.

[0892] R¹⁸, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

[0893] R¹⁹, at each occurrence, is independently selected from H,methyl, ethyl, propyl, and butyl; and

[0894] R²⁰ is H, methyl, or ethyl.

[0895] [19] In another preferred embodiment the present inventionprovides a compound of Formula (If) wherein:

[0896] L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

[0897] Ring C is selected from:

[0898] R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃,—CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂, —CH(OH)CH(CH₃)₂,—CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃, —CF₂CH₂CH(CH₃)₂,—CH(NHCH₃)CH₂CH(CH₃)₂, —CH (NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl-,cyclopentyl-, cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,1-NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,(3-F-phenyl)CH₂—(4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂-phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,(3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl) CH₂CH₂—,(3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,(2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,(2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—, phenyl-CH₂CH(OH)—,imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—;

[0899] W is a bond or —CH₂—;

[0900] X is a bond;

[0901] Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or—N(CH₃)—,

[0902] Z is methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl,s-butyl, t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl,2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl,2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl,2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl,3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl,3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl,2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl, furanyl, thienyl, pyridyl,2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl,isoxazolyl, 1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, morpholino, N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,(3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—,(4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—,(4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—,4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—,(4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—,(2-Me-pyridyl)CH₂—, (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—,(1-imidazolyl)CH₂—, (oxazolyl)CH₂—, (isoxazolyl)CH₂—,(1-benzimidazolyl)CH₂—, (cyclopropyl)CH₂—, (cyclobutyl)CH₂—,(cyclopentyl)CH₂—, (cyclohexyl)CH₂—, (morpholino)CH₂—,(N-pipridinyl)CH₂—, phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—,(2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—,(2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,(2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,(3-Cl-4-F-phenyl)CH₂CH₂—, (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—,(4-MeO-phenyl)CH₂CH₂—, (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—,(4-Me-phenyl)CH₂CH₂—, (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—,(4-MeS-phenyl)CH₂CH₂—, (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,(4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—,(thienyl)CH₂CH₂—,(pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,(4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,(isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—,(cyclopropyl)CH₂CH₂—,(cyclobutyl)CH₂CH₂—,(cyclopentyl)CH₂CH₂—,(cyclohexyl)CH₂CH₂—,(morpholino)CH₂CH₂—, or (N-pipridinyl)CH₂CH₂—; and

[0903] R¹¹, at each occurrence, is independently selected from H, ═O,methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl, (4-F-phenyl)CH₂—,(4-F-phenyl)CH₂CH₂—, 3-F-phenyl, (3-F-phenyl)CH₂—, (3-F-phenyl)CH₂CH₂—,2-F-phenyl, (2-F-phenyl)CH₂—, (2-F-phenyl)CH₂CH₂—, 4-Cl-phenyl,(4-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂CH₂—, 3-Cl-phenyl, (3-Cl-phenyl)CH₂—,(3-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,(4-CH₃-phenyl)CH₂CH₂—, 3-CH₃-phenyl, (3-CH₃-phenyl)CH₂—,(3-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—,(4-CF₃-phenyl)CH₂CH₂—, cyclopentyl, pyrid-2-yl, pyrid-3-yl, orpyrid-4-yl.

[0904] [20] In another preferred embodiment the present inventionprovides a compound of Formula (I) selected from:

[0905]{[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carboxamide;

[0906]{[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide;

[0907][(N-butylcarbamoyl)cyclopentyl]-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide;

[0908]2-(3,5-difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclohexyl}acetamide;

[0909]2-(3,5-difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}acetamide;

[0910]2-(3,5-difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopropyl}acetamide;

[0911]3-cyclopentyl-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclohexyl}propanamide;

[0912]2-(3,5-difluorophenyl)-N-{4-[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl](4-piperidyl)}acetamide;

[0913] phenyl4-[2-(3,5-difluorophenyl)acetylamino]-4-[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]piperidinecarboxylate;

[0914]4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;

[0915]N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}{[(phenylmethoxy)carbonylamino]cyclopentyl}carboxamide;

[0916](2S)-N-{[N-(1-{[3-(4-fluorophenoxy)phenyl]methyl}-2-oxoazaperhydroepin-3-yl)carbamoyl]cyclopropyl}-2-hydroxy-4-methylpentanamide;

[0917](2S)-N-{[N-(1-{[3-(4-fluorophenoxy)phenyl]methyl}-2-oxoazaperhydroepin-3-yl)carbamoyl]cyclopentyl}-2-hydroxy-3-methylbutanamide;

[0918]2,2-difluoro-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-4-phenylbutanamide;

[0919]N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-3-(4-piperidyl)propanamide;

[0920](2S)-2-hydroxy-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide;

[0921]3-cyclopropyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide;

[0922](2R)-2-hydroxy-3-imidazol-2-yl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide;

[0923]2-ethoxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide;

[0924]3-cyclopentyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide;

[0925](2S)-2-hydroxy-3-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]butanamide;

[0926](2S)-2-cyclohexyl-2-hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide;

[0927](2R)-2-cyclohexyl-2-hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide;

[0928](2S)-2-amino-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide;

[0929][(cyclohexylcarbonylamino)cyclopentyl]-N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carboxamide;

[0930]{[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carboxamide;

[0931]4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide;

[0932](2S)-2-hydroxy-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide;

[0933]3-methoxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide;

[0934](2S)-2-hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-3-phenylpropanamide;

[0935]N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-2-(phenylmethoxy)acetamide;

[0936](2S)-2-hydroxy-3-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}butanamide;

[0937](2S)-2-hydroxy-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;

[0938]3-cyclopentyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}propanamide;

[0939](2S)-2-cyclohexyl-2-hydroxy-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}acetamide;

[0940]3-cyclopropyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}propanamide;

[0941]N-{[N-(1-butyl-5-cyclopentyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}-4-methylpentanamide;

[0942]N-{[N-(5-cyclopentyl-1-methyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}-4-methylpentanamide;

[0943](2S)-2-hydroxy-3-methyl-N-({N-[2-oxo-1-benzyl(3H,4H,5H-benzo[f]azaperhydroepin-3-yl)]carbamoyl}cyclopentyl)butanamide;

[0944](2S)-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-2-[(propylsulfonyl)amino]pentanamide;

[0945](2S)-2-amino-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;

[0946]2,2-difluoro-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;

[0947]4-methyl-N-{[N-(6-oxo(5H,7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;

[0948]N-({N-[5-(3,3-dimethyl-2-oxobutyl)-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide;

[0949]4-methyl-N-[(N-{6-oxo-5-[(3-phenoxyphenyl)methyl](7H-dibenzo[d,f]azaperhydroepin-7-yl)}carbamoyl)cyclopentyl]pentanamide;

[0950]N-{[N-(5-butyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-4-methylpentanamide;

[0951]4-methyl-N-({N-[6-oxo-5-benzyl(7H-dibenzo[d,f]azaperhydroepin-7-yl)]carbamoyl}cyclopentyl)pentanamide;

[0952]N-({N-[5-(tert-butyl)-1-methyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide;

[0953]N-({N-[5-(tert-butyl)-1-butyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide;and

[0954]N-({N-[5-butyl-2-oxo-1-(2-pyridylmethyl)(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide.

[0955] In another embodiment the present invention provides for a methodfor the treatment of neurological disorders associated with β-amyloidproduction comprising administering to a host in need of such treatmenta therapeutically effective amount of a compound of Formula (I):

[0956] or a pharmaceutically acceptable salt or prodrug thereof.

[0957] It is understood that any and all embodiments of the presentinvention may be taken in conjunction with any other embodiment todescribe additional even more preferred embodiments of the presentinvention.

[0958] In a second embodiment, the present invention provides apharmaceutical composition comprising a compound of Formula (I) and apharmaceutically acceptable carrier.

[0959] In a third embodiment, the present invention provides a methodfor the treatment of neurological disorders associated with β-amyloidproduction comprising administering to a host in need of such treatmenta therapeutically effective amount of a compound of Formula (I).

[0960] In a preferred embodiment the neurological disorder associatedwith β-amyloid production is Alzheimer's Disease.

[0961] In a fourth embodiment, the present invention provides a methodfor inhibiting γ-secretase activity for the treatment of a physiologicaldisorder associated with inhibiting γ-secretase activity comprisingadministering to a host in need of such inhibition a therapeuticallyeffective amount of a compound of Formula (I) that inhibits γ-secretaseactivity.

[0962] Thus, the present invention provides a method for inhibitingγ-secretase activity comprising administering to a host in need of suchinhibition a therapeutically effective amount of a compound of Formula(I) that inhibits γ-secretase activity.

[0963] In a preferred embodiment the physiological disorder associatedwith inhibiting γ-secretase activity is Alzheimer's Disease.

[0964] In a fifth embodiment, the present invention provides a compoundof Formula (I) for use in therapy.

[0965] In a preferred embodiment the present invention provides acompound of Formula (I) for use in therapy of Alzheimer's Disease.

[0966] In a sixth embodiment, the present invention provides for the useof a compound of Formula (I) for the manufacture of a medicament for thetreatment of Alzheimer's Disease.

[0967] It is understood that any and all embodiments of the presentinvention may be taken in conjunction with any other embodiment todescribe additional even more preferred embodiments of the presentinvention.

DEFINITIONS

[0968] As used herein, the term “Aβ” denotes the protein designated Aβ,β-amyloid peptide, and sometimes β/A4, in the art. Aβ is anapproximately 4.2 kilodalton (kD) protein of about 39 to 43 amino acidsfound in amyloid plaques, the walls of meningeal and parenchymalarterioles, small arteries, capillaries, and sometimes, venules. Theisolation and sequence data for the first 28 amino acids are describedin U.S. Pat. No 4,666,829. The 43 amino acid sequence is: 1 Asp Ala GluPhe Arg His Asp Ser Gly Tyr 11 Glu Val His His Gln Lys Leu Val Phe Phe21 Ala Glu Asp Val Gly Ser Asn Lys Gly Ala 31 Ile Ile Gly Leu Met ValGly Gly Val Val 41 Ile Ala Thr

[0969] The term “AAP”, as used herein, refers to the protein known inthe art as β amyloid precursor protein. This protein is the precursorfor Aβ and through the activity of “secretase”enzymes, as used herein,it is processed into Aβ . Differing secretase enzymes, known in the art,have been designated β secretase, generating the N-terminus of Aβ, αsecretase cleaving around the 16/17 peptide bond in Aβ, and “γsecretases”, as used herein, generating C-terminal Aβ fragments endingat position 38, 39, 40, 42, and 43 or generating C-terminal extendedprecursors which are subsequently truncated to the above polypeptides.

[0970] The compounds herein described may have asymmetric centers.Compounds of the present invention containing an asymmetricallysubstituted atom may be isolated in optically active or racemic forms.It is well known in the art how to prepare optically active forms, suchas by resolution of racemic forms or by synthesis from optically activestarting materials. Many geometric isomers of olefins, C═N double bonds,and the like can also be present in the compounds described herein, andall such stable isomers are contemplated in the present invention. Cisand trans geometric isomers of the compounds of the present inventionare described and may be isolated as a mixture of isomers or asseparated isomeric forms. All chiral, diastereomeric, racemic forms andall geometric isomeric forms of a structure are intended, unless thespecific stereochemistry or isomeric form is specifically indicated.

[0971] The term “substituted,” as used herein, means that any one ormore hydrogens on the designated atom is replaced with a selection fromthe indicated group, provided that the designated atom's normal valencyis not exceeded, and that the substitution results in a stable compound.When a substituent is keto (i.e., ═O), then 2 hydrogens on the atom arereplaced.

[0972] When any variable (e.g., R^(5b)) occurs more than one time in anyconstituent or formula for a compound, its definition at each occurrenceis independent of its definition at every other occurrence. Thus, forexample, if a group is shown to be substituted with 0-2 R^(5b), thensaid group may optionally be substituted with up to two R^(5b) groupsand R^(5b) at each occurrence is selected independently from thedefinition of R^(5b). Also, combinations of substituents and/orvariables are permissible only if such combinations result in stablecompounds.

[0973] When a bond to a substituent is shown to cross a bond connectingtwo atoms in a ring, then such substituent may be bonded to any atom onthe ring. When a substituent is listed without indicating the atom viawhich such substituent is bonded to the rest of the compound of a givenformula, then such substituent may be bonded via any atom in suchsubstituent. Combinations of substituents and/or variables arepermissible only if such combinations result in stable compounds.

[0974] As used herein, “alkyl” or “alkylene” is intended to include bothbranched and straight-chain saturated aliphatic hydrocarbon groupshaving the specified number of carbon atoms; for example, “C₁-C₆ alkyl”denotes alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms. Examples of alkylinclude, but are not limited to, methyl, ethyl, n-propyl, i-propyl,n-butyl, i-butyl, sec-butyl, t-butyl, pentyl, and hexyl. Preferred“alkyl” group, unless otherwise specified, is “C₁-C₄ alkyl”.Additionally, unless otherwise specified, “propyl” denotes n-propyl ori-propyl; “butyl” denotes n-butyl, i-butyl, sec-butyl, or t-butyl.

[0975] As used herein, “alkenyl”, or “alkenylene” is intended to includehydrocarbon chains of either a straight or branched configuration andone or more unsaturated carbon-carbon bonds which may occur in anystable point along the chain. Examples of “C₂-C₆ alkenyl” include, butare not limited to, ethenyl, 1-propenyl, 2-propenyl, 1-butenyl,2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 2-pentenyl, 3-pentenyl,hexenyl, and the like.

[0976] As used herein, “alkynyl”, or “alkynylene” is intended to includehydrocarbon chains of either a straight or branched configuration andone or more carbon-carbon triple bonds which may occur in any stablepoint along the chain, such as ethynyl, 1-propynyl, 2-propynyl,1-butynyl, 2-butynyl, 3-butynyl, and the like.

[0977] “Alkoxy” or “alkyloxy” represents an alkyl group as defined abovewith the indicated number of carbon atoms attached through an oxygenbridge. Examples of alkoxy include, but are not limited to, methoxy,ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy,and s-pentoxy. Preferred alkoxy groups are methoxy, ethoxy, n-propoxy,i-propoxy, n-butoxy, s-butoxy, t-butoxy. Similarly, “alkylthio” or“thioalkoxy” is represents an alkyl group as defined above with theindicated number of carbon atoms attached through a sulphur bridge.

[0978] “Halo” or “halogen” as used herein refers to fluoro, chloro,bromo, and iodo. Unless otherwise specified, preferred halo is fluoroand chloro. “Counterion” is used to represent a small, negativelycharged species such as chloride, bromide, hydroxide, acetate, sulfate,and the like.

[0979] “Haloalkyl” is intended to include both branched andstraight-chain saturated aliphatic hydrocarbon groups having thespecified number of carbon atoms, substituted with 1 or more halogen(for example —C_(v)F_(w) where v=1 to 3 and w=1 to (2v+1)). Examples ofhaloalkyl include, but are not limited to, trifluoromethyl,trichloromethyl, pentafluoroethyl, pentachloroethyl,2,2,2-trifluoroethyl, 2,2-difluoroethyl, heptafluoropropyl, andheptachloropropyl. “Haloalkoxy” is intended to mean a haloalkyl group asdefined above with the indicated number of carbon atoms attached throughan oxygen bridge; for example trifluoromethoxy, pentafluoroethoxy,2,2,2-trifluoroethoxy, and the like. “Halothioalkoxy” is intended tomean a haloalkyl group as defined above with the indicated number ofcarbon atoms attached through a sulphur bridge.

[0980] “Cycloalkyl” is intended to include saturated ring groups, havingthe specified number of carbon atoms. For example, “C₃-C₆ cycloalkyl”denotes such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0981] As used herein, “carbocycle” is intended to mean any stable 3- to7-membered monocyclic or bicyclic or 7- to 13-membered bicyclic ortricyclic, any of which may be saturated, partially unsaturated, oraromatic. Examples of such carbocycles include, but are not limited to,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,adamantyl, cyclooctyl, [3.3.0]bicyclooctane, [4.3.0]bicyclononane,[4.4.0]bicyclodecane (decalin), [2.2.2]bicyclooctane, fluorenyl, phenyl,naphthyl, indanyl, adamantyl, or tetrahydronaphthyl (tetralin).Preferred “carbocycle” are cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

[0982] As used herein, the term “heterocycle” or “heterocyclic ring” isintended to mean a stable 5- to 7-membered monocyclic or bicyclic or 7-to 14-membered bicyclic heterocyclic ring which is saturated partiallyunsaturated or unsaturated (aromatic), and which consists of carbonatoms and 1, 2, 3 or 4 heteroatoms independently selected from the groupconsisting of N, O and S and including any bicyclic group in which anyof the above-defined heterocyclic rings is fused to a benzene ring. Thenitrogen and sulfur heteroatoms may optionally be oxidized. Theheterocyclic ring may be attached to its pendant group at any heteroatomor carbon atom which results in a stable structure. The heterocyclicrings described herein may be substituted on carbon or on a nitrogenatom if the resulting compound is stable. If specifically noted, anitrogen in the heterocycle may optionally be quaternized. It ispreferred that when the total number of S and O atoms in the heterocycleexceeds 1, then these heteroatoms are not adjacent to one another. It ispreferred that the total number of S and O atoms in the heterocycle isnot more than 1.

[0983] Examples of heterocycles include, but are not limited to,1H-indazole, 2-pyrrolidonyl, 2H,6H-1,5,2-dithiazinyl, 2H-pyrrolyl,3H-indolyl, 4-piperidonyl, 4aH-carbazole, 4H-quinolizinyl,6H-1,2,5-thiadiazinyl, acridinyl, azocinyl, benzimidazolyl,benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl,benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl,benzisothiazolyl, benzimidazalonyl, carbazolyl, 4aH-carbazolyl,b-carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl,2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl,furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl,indolenyl, indolinyl, indolizinyl, indolyl, isobenzofuranyl,isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl,isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl,octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl,oxazolyl, oxazolidinylperimidinyl, phenanthridinyl, phenanthrolinyl,phenarsazinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl,phthalazinyl, piperazinyl, piperidinyl, pteridinyl, piperidonyl,4-piperidonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl,pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole,pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl,pyrrolinyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl,quinoxalinyl, quinuclidinyl, carbolinyl, tetrahydrofuranyl,tetrahydroisoquinolinyl, tetrahydroquinolinyl, 6H-1,2,5-thiadiazinyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl,thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl,1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl,xanthenyl. Preferred 5 to 10 membered heterocycles include, but are notlimited to, pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl,thiazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,tetrazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl,1H-indazolyl, oxazolidinyl, isoxazolidinyl, benzotriazolyl,benzisoxazolyl, oxindolyl, benzoxazolinyl, quinolinyl, andisoquinolinyl. Preferred 5 to 6 membered heterocycles include, but arenot limited to, pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl,thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl,oxazolyl, isoxazolyl, tetrazolyl; more preferred 5 to 6 memberedheterocycles include, but are not limited to, pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, piperazinyl, piperidinyl,pyrazolyl, imidazolyl, and tetrazolyl. Also included are fused ring andspiro compounds containing, for example, the above heterocycles.

[0984] As used herein, the term “aryl”, “C₆-C₁₀ aryl” or aromaticresidue, is intended to mean an aromatic moiety containing the specifiednumber of carbon atoms; for example phenyl, pyridinyl or naphthyl.Preferred “aryl” is phenyl. Unless otherwise specified, “aryl” may beunsubstituted or substituted with 0 to 3 groups selected from H, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, amino, hydroxy,Cl, F, Br, I, CF₃, SCH₃, S(O)CH₃, SO₂CH₃, —N(CH₃)₂, N(CH₃)H, CN, NO₂,OCF₃, C((═O)CH₃, CO₂H, CO₂CH₃, or C₁-C₄ haloalkyl.

[0985] The phrase “additional lactam carbons”, as used herein, isintended to denote the number of optional carbon atoms in the lactamring B of Formula (I). Formula (I″):

[0986] represents the lactam ring B of Formula (I). Additional lactamcarbons are carbons in lactam ring B other than the carbons numbered 2and 3 in the backbone of the formula. The additional lactam carbons maybe optionally replaced by a heteroatom selected from oxygen, nitrogenand sulfur. Lactam ring B contains 1, 2, 3, 4, 5, 6 or 7 optionalcarbons, wherein one optional carbon may optionally be replaced by aheteroatom, such that the total number of members of lactam ring B,including atoms numbered 1, 2 and 3 in the backbone, does not exceed 10.It is preferred that the total number of atoms of lactam ring B is 6, 7or 8; it is more preferred that the total number of atoms of lactam ringB is seven. It is further understood that lactam ring B may optionallybe unsaturated or partially unsaturated (i.e. two adjacent atoms in thering form a double bond) wherein the backbone of lactam ring B maycontain one, two or three double bonds. Examples of lactam ring Binclude:

[0987] but are not intended to limit the invention. Preferred examplesof lactam ring B are B1, B2, B5, B6, B8, B9, B13, and B16; morepreferred examples of lactam ring B are B1, B6, B8, B9, and B13.Preferred examples of substituent R¹⁰ or R¹¹ on lactam B are methyl,ethyl, phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-trifluoromethylphenyl,(4-fluorophenyl)methyl, (4-chlorophenyl)methyl,(4-trifluoromethylphenyl)methyl, and 2-, 3-, and 4-pyridinyl. Preferredexamples of R¹³ on lactam B are F, Cl, OH, methyl, ethyl, methoxy, andtrifluoromethyl.

[0988] The compounds herein described may have asymmetric centers. Oneenantiomer of a compound of Formula (I) may display superior biologicalactivity over the opposite enantiomer. For example carbon 3 of lactamring B Formula (I″) may exist in either an S or R configuration. Thus,an R or S configuration at carbon 3 in Formula (I″) is considered partof the invention. An example of such configuration includes,

[0989] but is not intended to be limited to this example of ring B. Whenrequired, separation of the racemic material can be achieved by methodsknown in the art.

[0990] The phrase “pharmaceutically acceptable” is employed herein torefer to those compounds, materials, compositions, and/or dosage formswhich are, within the scope of sound medical judgment, suitable for usein contact with the tissues of human beings and animals withoutexcessive toxicity, irritation, allergic response, or other problem orcomplication, commensurate with a reasonable benefit/risk ratio.

[0991] As used herein, “pharmaceutically acceptable salts” refer toderivatives of the disclosed compounds wherein the parent compound ismodified by making acid or base salts thereof. Examples ofpharmaceutically acceptable salts include, but are not limited to,mineral or organic acid salts of basic residues such as amines; alkalior organic salts of acidic residues such as carboxylic acids; and thelike. The pharmaceutically acceptable salts include the conventionalnon-toxic salts or the quaternary ammonium salts of the parent compoundformed, for example, from non-toxic inorganic or organic acids. Forexample, such conventional non-toxic salts include those derived frominorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic,phosphoric, nitric and the like; and the salts prepared from organicacids such as acetic, propionic, succinic, glycolic, stearic, lactic,malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic,phenylacetic, glutamic, benzoic, salicylic, sulfanilic,2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethanedisulfonic, oxalic, isethionic, and the like.

[0992] The pharmaceutically acceptable salts of the present inventioncan be synthesized from the parent compound which contains a basic oracidic moiety by conventional chemical methods. Generally, such saltscan be prepared by reacting the free acid or base forms of thesecompounds with a stoichiometric amount of the appropriate base or acidin water or in an organic solvent, or in a mixture of the two;generally, nonaqueous media like ether, ethyl acetate, ethanol,isopropanol, or acetonitrile are preferred. Lists of suitable salts arefound in Remington's Pharmaceutical Sciences, 17th ed., Mack PublishingCompany, Easton, Pa., 1985, p. 1418, the disclosure of which is herebyincorporated by reference.

[0993] “Prodrugs” are intended to include any covalently bonded carrierswhich release the active parent drug according to formula (I) in vivowhen such prodrug is administered to a mammalian subject. Prodrugs of acompound of formula (I) are prepared by modifying functional groupspresent in the compound in such a way that the modifications arecleaved, either in routine manipulation or in vivo, to the parentcompound. Prodrugs include compounds of formula (I) wherein a hydroxy,amino, or sulfhydryl group is bonded to any group that, when the prodrugor compound of formula (I) is administered to a mammalian subject,cleaves to form a free hydroxyl, free amino, or free sulfhydryl group,respectively. Examples of prodrugs include, but are not limited to,acetate, formate and benzoate derivatives of alcohol and aminefunctional groups in the compounds of formula (I), and the like.

[0994] “Stable compound” and “stable structure” are meant to indicate acompound that is sufficiently robust to survive isolation to a usefuldegree of purity from a reaction mixture, and formulation into anefficacious therapeutic agent.

SYNTHESIS

[0995] The compounds of the present invention can be prepared in anumber of ways well known to one skilled in the art of organicsynthesis. The compounds of the present invention can be synthesizedusing the methods described below, together with synthetic methods knownin the art of synthetic organic chemistry, or variations thereon asappreciated by those skilled in the art. Preferred methods include, butare not limited to, those described below. All references cited hereinare hereby incorporated in their entirety herein by reference.

[0996] The novel compounds of this invention may be prepared using thereactions and techniques described in this section. The reactions areperformed in solvents appropriate to the reagents and materials employedand which are suitable for the transformations being effected. Also, inthe description of the synthetic methods described below, it is to beunderstood that all proposed reaction conditions, including choice ofsolvent, reaction atmosphere, reaction temperature, duration of theexperiment and work-up procedures, are chosen to be the conditionsstandard for that reaction, which should be readily recognized by oneskilled in the art. It is understood by one skilled in the art oforganic synthesis that the functionality present on various portions ofthe molecule must be compatible with the reagents and reactionsproposed. Such restrictions to the substituents which are compatiblewith the reaction conditions will be readily apparent to one skilled inthe art and alternate methods must then be used.

[0997] In a preferred method of synthesis, the compounds of Formula (I)of the present invention can be prepared from carboxylic acid 1 andamine 2 using amide bond syntheses known in the art, including methodscommonly used in peptide syntheses, such as HATU, TBTU, BOP, EDC, CDI,and DCC-mediated couplings, as illustrated in Scheme 1. Depending on thestructure of the final product, it is appreciated by those skilled inthe art that protecting groups or precursor functionality convertible tothe desired groups may be desirable. Protecting groups and their use insynthesis are described in Green and Wuts, Protective Groups in OrganicSynthesis, (Wiley 1991).

[0998] Additionally, the syntheses of a representative malonamide and arepresentative acetamide of Formula (I) are illustrated in Scheme 2 andScheme 3, respectively. As will be readily apparent to those of ordinaryskill in the art, the synthetic procedure illustrated in Scheme 2 and 3,and the reaction conditions described below can be modified by selectingthe appropriate starting materials and reagents to allow the preparationof other compounds of the present invention.

[0999] Methods for the synthesis of lactams useful as intermediates inthe synthesis of compounds of the present invention, including aminobisbenzodiazepine 5 and amino benzodiazepine 8, are known in the art andare disclosed in a number of references including PCT publication numberWO 98/28268, WO 99/66934, and WO 00/07995, which are hereby incorporatedby reference. Additional references include Bock, et. al., J. Org.Chem., 1987, 52, 3232-3239; Sherrill et. al., J. Org. Chem., 1995, 60,730-734; Walsh, D. A., Synthesis, September 1980, p. 677; and Brown, at.al., Tetrahedron Letters, 1971, 8, 667-670.

[1000] Cyclic carboxylic acid intermediates, such as 4, are useful forthe synthesis of the current invention, and may be synthesized by anumber of ways well known in the art. One of the preferred syntheses ofthe compounds of this invention is shown in Scheme 4. Typically aconvergent route is employed, which joins the acid 11 and the aminetogether to afford the key intermediate 12 using standard bond-formingprocedures (Synthesis 1989, 37-38). The desired carboxylic acid 4 may beprepared from the known malonate ester 10 (e.g. Chung, S. K. Korean J.Med. Chem. 1995, 5, 94-111) via a three-step protocol as shown in Scheme4.

[1001] One of the preferred syntheses of cyclic amino acids, such as 7which is useful in the preparation of compounds of Formula (I), isoutlined in Scheme 5. As illustrated for the synthesis of carboxylicacid 7, the desired intermediate ester 18 is prepared by the initialcoupling reaction of acid 14 and amine 13 under standard conditionsusing EDC and HOBt. Both the acids and the amines employed as startingmaterials in this invention are either commercially available or can beprepared from commercially available materials using conventionalprocedures and reagents. As apparent to those of ordinary skill in theart, the synthetic procedure illustrated in Scheme 5 and the reactionconditions described will allow the preparation of many other analogs of7 by selecting the appropriate starting materials and reagents.

[1002] Methods for the synthesis of lactams useful as intermediates inthe synthesis of compounds of the present invention are known in the artand are disclosed in a number of references including PCT publicationnumber WO 98/28268, WO 99/66934, and WO00/07995, which are herebyincorporated by reference. Additional references include Bock, et. al.,J. Org. Chem., 1987, 52, 3232-3239; Sherrill et. al., J. Org. Chem.,1995, 60, 730-734; Walsh, D. A., Synthesis, September 1980, p. 677; andBrown, at. al., Tetrahedron Letters, 1971, 8, 667-670.

[1003] One of the preferred syntheses of the lactam intermediates, suchas 23, is outlined in Scheme 6.

[1004] a) Preparation of 21

[1005] To a suspension of 19 (30.0 g, 155 mmol) in dry Et₂O (300 mL)under N₂ at −70° C. was added t-BuLi (205 mL, 1.7 M in pentane) andstirred for 4 h between −20° C. and −10° C. The reaction was cooled to−70° C. and transferred via canula to a round bottom containing 20 (23.0mL, 186 mmol) in dry Et₂O (150 mL) under N₂ at −70° C. The reaction wasstirred while warming to rt for 14 h and quenched with 20% citric acid.The resulting layers were separated and the organic layer was washedwith sat. NaHCO₃, brine, dried over Na₂SO₄, filtered and concentrated togive a yellow oil. The oil was dissolved in EtOH-HCl (200 mL) andstirred overnight. The solvent was removed in vacuo at 70° C. and theresulting oil triturated with Et₂O. The resultant solid was filtered andwashed with Et₂O to afford 21 HCl (23.9 g, 64%) as a orange solid: ¹HNMR (500 MHz, CD₃OD) δ8.10 (d, 1 H), 7.66 (t, 1 H), 7.56 (t, 1 H), 7.51(d, 1 H), 1.41 (s, 9 H); ESI MS m/z=178 [C₁₁H₁₅NO+H]⁺.

[1006] The orange solid was dissolved in 1N NaOH and EtOAC and thelayers were separated. The organic layer was washed with brine, driedover Na₂SO₄, filtered and concentrated to afford 21 (21 g, 99%) as ayellow oil: ¹H NMR (500 MHz, CD₃OD) δ7.70 (d, 1 H), 7.16 (t, 1 H), 6.78(d, 1 H), 6.59 (t, 1 H), 1.38 (s, 9 H).

[1007] b) Preparation of Example 23

[1008] To a solution of 22 (5.5 g, 17.0 mmol) in dry THF (50 mL) at 0°C. was added oxalyl chloride (1.47 mL, 17.0 mmol) and DMF (0.2 mL) andstirred for 1.25 h. A solution of 21 (3.3 g, 15.4 mmol) andN-methylmorpholine (4.7 mL, 42.4 mmol) in dry THF (20 mL) was added tothe reaction dropwise and the reaction was stirred at rt for 1.5 h. Thereaction was filtered and MeOH (100 mL) and NH₄OH (50 mL) was added tothe filtrate and the reaction was sealed. After 45 min, the reaction wasconcentrated to half its volume and added dropwise to a cooled solution(15° C.) of ammonium acetate (5.75 g) in acetic acid (120 ml). Thereaction was stirred over night at rt, dissolved in Et₂O (100 mL), madebasic with 6 N NaOH, and cooled in ice while stirring for 1 h. Theresulting solid was filtered, washed with H₂O and Et₂O, and dried in avacuum oven at 30° C. to afford 23 (3.5 g, 63%) as a white solid: ¹H NMR(500 MHz, CD₃OD) δ7.78-7.16 (m, 10 H), 5.12 (s, 2 H), 1.27 (s, 9 H).

[1009] Abbreviations used in the description of the chemistry and in theexamples that follow are: Ac acetyl or acetate aq aqueous Bn benzyl Boct-butyloxycarbonyl Cbz benzyloxycarbonyl DIEA N,N′-diisopropylethylamineDMAP 4-dimethylaminopyridine DME ethylene glycol dimethyl ether DMFN,N′-dimethylformamide DMSO dimethylsulfoxide or methyl sulfoxideEDC•HCl 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HOBTl-hydroxybenzotriazole HPLC high performance liquid chromatographyLiHMDS lithium hexamethyldisilazide MeCN acetonitrile MS massspectrometry satd saturated rt or RT room temperature TFAtrifluoroacetic acid THF tetrahydrofuran TLC thin layer chromatography

EXAMPLES

[1010] The examples provided are intended to assist in a furtherunderstanding of the invention. Particular materials employed, speciesand conditions are intended to be further illustrate of the inventionand not limit the reasonable scope thereof.

[1011] Compounds of the present invention are generally purified by HPLCusing conditions known to one skilled in the art. However, unlessotherwise indicated, the following conditions are generally applicable.HPLC Condition A: reverse-phase HPLC can be carried out using a VydacC-18 column with gradient elution from 10% to 100% buffer B in buffer A(buffer A: water containing 0.1% trifluoroacetic acid, buffer B: 10%water, 90% acetonitrile containing 0.1% trifluoroacetic acid).Alternatively: HPLC Condition B: reverse-phase HPLC can be carried outusing a Vydac C-18 column with gradient elution from 10% to 90%acetonitrile in water.

Example 1{[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carboxamide

[1012]

[1013] (a) Methyl 1-[N-(3-methylbutyl)carbamoyl]cyclopentanecarboxylate

[1014] To 1-(methoxycarbonyl)cyclopentanecarboxylic acid (630 mg, 3.7mmol) in CH₂Cl₂/DMF (5:1, 37 mL) at 0° C. was added HOBT (730 mg, 4.8mmol) and EDC (920 mg, 4.8 mmol). The mixture was stirred for 10 minthen 3-methylbutylamine (640 mg, 7.4 mmol) was added and stirring wascontinued for 1 h. The solution was poured into water and the layersseparated. The aqueous layer was extracted with methylene chloride andthe combined extracts were washed with water, 1N HCl, sat'd NaHCO₃,dried over magnesium sulfate, and concentrated to a glassy solid (800mg, 90%). MS [M+H]⁺243.

[1015] (b) Methyl 1-[N-(3-methylbutyl)carbamoyl]cyclopentanecarboxylicacid

[1016] To a solution of methyl l-[N-(3-methylbutyl)carbamoyl]cyclopentanecarboxylate (820 mg, 3.4 mmol) in 25 mL of THF cooled to 0°C. was added dropwise a solution of lithium hydroxide monohydrate (260mg, 6.12 mmol) in 5.0 mL of water. The reaction mixture was stirred atrt for 16 h. THF was removed under reduced pressure to give a yellow oilwhich was diluted with 10 mL of 1N HCl. The aqueous phase was extractedwith CH₂Cl₂ (8×15 mL), and the extracts were combined, dried overNa₂SO₄, and concentrated to afford 700 mg (90%) of methyl1-[N-(3-methylbutyl)carbamoyl]-cyclopentanecarboxylic acid as a whitesolid. MS [M+H]⁺228.

[1017] (c){[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carboxamide

[1018] To 1-[N-(3-methylbutyl)carbamoyl]cyclopentane carboxylic acid (38mg, 0.16 mmol) in CH₂Cl₂/DMF (5:1, 15 mL) at 0° C. was added HOBT (28mg, 0.18 mmol) and EDC (34 mg, 0.18 mmol). The mixture was stirred for10 min then 7-amino-5-methyl-7H-dibenzoazaperhydroepin-6-one (40 mg,0.16 mmol) (obtained as the first eluting peak of a racemic mixture on aCHIRALCEL OD column with 20% iPrOH/Hexane with diethylamine) was addedand stirring was continued for 1 h. The solution was poured into waterand the layers separated. The aqueous layer was extracted with methylenechloride and the combined extracts were washed with water, 1N HCl, sat'dNaHCO₃, dried over magnesium sulfate, and concentrated to a glassy solid(67 mg, 94%). ¹H NMR (300 MHz, CD₃OD) δ7.20-7.80 (m, 9H), 6.25 (m, 1H),5.25 (d, 1H), 3.38 (s, 3H), 3.27 (m, 1H), 2.58-2.05 (m, 5H), 1.80-1.25(m, 8H), 0.95, (m, 6H) MS [M+H]⁺448.

Example 2{[N-(3-Methylbutyl)carbamoyl]cyclopentyl}-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide

[1019]

[1020] The title compound was prepared in a manner similar to thatdescribed for Example 1. The product was obtained as a solid. MS[M+H]⁺475.

Example 3[(N-Butylcarbamoyl)cyclopentyl]-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide

[1021]

[1022] The title compound was prepared in a manner similar to thatdescribed for Example 1. The product was obtained as a solid. MS[M+H]⁺461.

Example 42-(3,5-Difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclohexyl}-acetamide

[1023]

[1024] (a){[(tert-Butoxy)carbonylamino]cyclohexyl}-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide

[1025] Diisopropylethylamine (2.5 mL, 15.0 mmol) and HATU (2.85 g, 7.5mmol) were added to a solution ofl-[(tert-butoxy)carbonylamino]cyclohexanecarboxylic acid (1.75 g, 7.2mmol) in CH₂Cl₂ (10 mL) at 0° C and stirred for 10 min.(S)-3-amino-1-methyl-5-phenyl-3H-benzoazepin-2-one (3.0 g, 6.0 mmol) wasthen added. The solution was allowed to warm to room temperature andstirred overnight. The reaction was quenched with water. The organiclayer was separated and washed with a saturated solution of NaHCO₃, 20%citric acid, brine, dried over Na₂SO₄, filtered and concentrated toafford a white solid (2.98 g, 99%). This compound underwent no furtherpurification: ¹H NMR (500 MHz, CD₃OD) δ7.33-7.13 (m, 9 H), 5.35 (s, 1H), 3.48 (s, 3 H), 2.21-1.29 (m, 10 H), 1.50, (s, 9 H).

[1026] (b)(Aminocyclohexyl)-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide

[1027] A saturated solution of HCl in EtOAc (50 mL) was added to asolution of{[(tert-butoxy)carbonylamino]cyclohexyl}-(S)-3-N-(1-methyl-2-oxo-5-phenyl(3H-benzoazepin-3-yl))carboxamide(2.9 g, 5.9 mmol) in EtOAc (75 mL) and stirred at room temperatureovernight. The reaction was quenched with 1N NaOH (100 mL). The organiclayer was separated, and the aqueous layer was extracted with EtOAc. Theorganic layers were combined, washed with brine, dried over Na₂SO₄,filtered and concentrated to give a white solid (1.76 g, 77%). mp106-110° C.; ¹H NMR (500 MHz, CD₃OD) δ7.33-7.13 (m, 9 H), 5.32 (s, 1 H),3.48 (s, 3 H), 1.98-1.25 (m, 10 H); CI MS m/z=391 [C₂₃H₂₆N₄O₂+H]⁺; HPLC100%, t_(r)=9.17 min. (HPLC Conditions A).

[1028] (c)2-(3,5-Difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]-cyclohexyl}acetamide

[1029] Diisopropylethylamine (0.87 ml, 5.15 mmol) and HATU (979 mg, 2.58mmol) were added to a solution of 2-(3,5-difluorophenyl)acetic acid (426mg, 2.47 mmol) in CH₂Cl₂ (40 mL) at 0° C. and stirred for 5 min.(Aminocyclohexyl)-(S)-3-N-(1-methyl-2-oxo-5-phenyl(3H-benzoazepin-3-yl))carboxamide(800 mg, 2.06 mmol) was then added, and the solution was allowed to warmto room temperature and stirred overnight. The reaction was quenchedwith water. The organic layer was separated and washed with a saturatedsolution of NaHCO₃, 20% citric acid, brine, dried over Na₂SO₄, filteredand concentrated to give a white solid. Further purification by flashcolumn chromatography afforded the title compound (659 mg, 60%) as awhite solid: mp 126-129° C; ¹H NMR (500 MHz, CD₃OD) δ7.72-7.32 (m, 9 H),6.97 (d, 2 H), 6.80 (t, 1 H), 5.31 (s, 1 H), 3.70 (s, 2 H), 3.48 (s, 3H), 2.24-1.30 (m 10 H); API MS m/z=545 [C₃₁H₃₀F₂N₄O₃+H]⁺; HPLC 99.5%,t_(r)=22.26 min. (HPLC Conditions A).

Example 52-(3,5-Difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}-acetamide

[1030]

[1031] The title compound was prepared in a manner similar to thatdescribed for Example 4. The product was obtained as a solid. mp112-117° C.; ¹H NMR (500 MHz, CD₃OD) δ7.72-7.31(m, 9 H), 6.96 (d, 2 H),6.81 (t, 1 H) 5.33 (s, 1 H), 3.63 (s, 2 H), 3.47 (s, 3 H), 2.41-1.72 (m,8 H); API MS m/z=531 [C₃₀H₂₈F₂N₄O₃+H]⁺; HPLC 99.4%, t_(r)=21.23 min.(HPLC Conditions A).

Example 62-(3,5-Difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopropyl}-acetamide

[1032]

[1033] The title compound was prepared in a manner similar to thatdescribed for Example 4. The product was obtained as a solid. mp212-214° C.; ¹H NMR (500 MHz, CD₃OD) δ7.71-7.30 (m, 9 H), 6.98 (d, 2 H),6.81 (t, 1 H), 5.28 (s, 1 H), 3.65 (s, 2 H), 3.48 (s, 3 H), 1.48 (m, 2H), 1.08 (m, 2 H); API MS m/z=503 [C₂₈H₂₄F₂N₄O₃+H]⁺; HPLC 97.7%,t_(r)=19.48 min. (HPLC Conditions A).

Example 73-Cyclopentyl-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclohexyl}propanamide

[1034]

[1035] The title compound was prepared in a manner similar to thatdescribed for Example 4. The product was obtained as a solid. mp 88-103°C.; ¹H NMR (500 MHz, CD₃OD) δ7.71-7.30 (m, 9 H), 5.28 (d, 1 H), 3.51 (d,3 H), 2.39-0.82 (m, 23 H); CI MS m/z=516 [C₃₁H₃₈N₄O₃+H]⁺; HPLC 96.5%,t_(r)=14.79 min. (HPLC Conditions A).

Example 82-(3,5-Difluorophenyl)-N-{4-[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl](4-piperidyl)}acetamide

[1036]

[1037] The title compound was prepared in a manner similar to thatdescribed for Example 4. The product was obtained as an oil. ¹H NMR (300MHz, CD₃OD) δ7.15-7.60 (m, 10H), 6.05-6.80 (m, 3H), 5.40 (d, 1H), 3.60(s, 2H), 3.40 (s, 3H), 2.90 (m, 2H), 2.60 (m, 2H), 2.05, (m, 4H). MS[M+H]⁺546.

Example 9

[1038] Phenyl4-[2-(3,5-difluorophenyl)acetylamino]-4-[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]piperidinecarboxylate

[1039] The title compound was prepared in a manner similar to thatdescribed for Example 4. The product was obtained as an oil. ¹H NMR (300MHz, CD₃OD) δ7.20-7.40 (m, 15H), 6.45-6.80 (m, 3H), 5.40 (d, 1H), 5.15(s, 2H), 4.85 (s, 3H), 3.85 (m, 1H), 3.60 (s, 2H), 3.40 (s, 3H), 2.20,(m, 4H). MS [M+H]⁺680.

Example 104-Methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide

[1040]

[1041] The title compound was prepared in a manner similar to thatdescribed for Example 4. This compound was made from the aminobisbenzazepine obtained as the first eluting peak of a racemic mixtureon a CHIRALCEL OD column with 20% iPrOH/Hexane with diethylamine. Theproduct was obtained as an oil. ¹H NMR (300 MHz, CD₃OD) δ7.20-7.60 (m,8H), 6.59 (s, 1H), 5.20 (d, 1H), 3.40 (s, 3H), 2.40-1.60 (m, 13H), 0.9,(d, 6H). MS [M+H]⁺448.

Example 11N-{1-Methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}{[(phenylmethoxy)carbonylamino]-cyclopentyl}carboxamide

[1042]

[1043] The title compound was prepared in a manner similar to thatdescribed for Example 4. This compound was made from the correspondingamino benzodiazepine that, as the CBz protected form, was the firsteluting peak of the racemic mixture on a CHIRALCEL AD column usingacetonitrile. The product was obtained as an oil. ¹H NMR (300 MHz,CD₃OD) δ7.20-7.40 (m, 13H), 5.2 (s, 2H), 5.60 (m, 1H), 5.40 (d, 1H),5.15 (s, 2H), 3.45 (s, 3H), 2.40 (m, 2H), 2.05-1.80 (m, 6H). MS[M+H]⁺579.

Example 12(2S)-N-{[N-(1-{[3-(4-Fluorophenoxy)phenyl]methyl}-2-oxoazaperhydroepin-3-yl)carbamoyl]cyclopropyl}-2-hydroxy-4-methylpentanamide

[1044]

[1045] The title compound was prepared in a manner similar to thatdescribed for Example 4. The product was obtained as an oil. ¹H NMR (300MHz, CD₃OD) δ7.00-6.70 (m, 8H), 4.45 (m, 5H), 4.15 (m, 1H), 3.10-3.40(m, 2H), 2.00-1.00 (m, 12H), 0.90, (m, 6H). MS [M+H]⁺526.

Example 13(2S)-N-{[N-(1-{[3-(4-Fluorophenoxy)phenyl]methyl}-2-oxoazaperhydroepin-3-yl)carbamoyl]cyclopentyl}-2-hydroxy-3-methylbutanamide

[1046]

[1047] The title compound was prepared in a manner similar to thatdescribed for Example 4. The product was obtained as an oil. ¹H NMR (300MHz, CD₃OD) δ7.20-6.80 (m, 8H), 4.60 (m, 3H), 4.00 (d, 1H), 3.5 (m, 1H),3.20 (m, 1H), 2.40-1.05 (m, 17H), 1.00 (d, 3H), 0.90 (d, 3H). MS[M+H]⁺540.

Example 142,2-Difluoro-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-4-phenylbutanamide

[1048]

[1049] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H NMR (300 MHz, CD₃OD)δ7.90-7.00 (m, 13H), 5.45 (d, 1H), 3.45 (s, 3H), 2.80 (m, 2H), 2.60-2.20(m, 6H), 1.80-1.90 (m, 8H). MS [M+H]⁺627.

Example 15N-[(N-{1-Methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-3-(4-piperidyl)propanamide

[1050]

[1051] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H NMR (300 MHz, CD₃OD)δ8.00-7.20 (m, 9H), 6.10 (s, 1H), 5.40 (d, 1H), 5.15 (s, 2H), 3.60 (m,1H), 3.40 (s, 3H), 3.15 (m, 1H), 2.60-1.20 (m, 14H). MS [M+H]⁺584.

Example 16(2S)-2-Hydroxy-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide

[1052]

[1053] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. MS [M+H]⁺559.

Example 173-Cyclopropyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]l,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide

[1054]

[1055] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H NMR (300 MHz, CD₃OD)δ7.60-7.20 (m, 8H), 5.40 (m, 1H), 3.45 (s, 3H), 2.70 (s, 2H), 2.40 (m,4H), 2.05-1.09 (m, 14H), 0.4 (m, 1H), 0.00 (m, 1H). MS [M+H]⁺541.

Example 18(Aminocyclopentyl)-N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carboxamide

[1056]

[1057] The title compound was prepared in a manner similar to thatdescribed for Example 4. This compound was made from the BZD amine that,as a CBz protected form, was the first peak of the racemic mixture onthe CHIRALCEL AD column with acetonitrile. The product was obtained asan oil. ¹H NMR (300 MHz, CD₃OD) δ7.20-7.80 (m, 8H), 5.45 (m, 1H), 3.45(s, 3H), 2.20 (m, 3H), 2.00-1.60 (m, 5H). MS [M+H]⁺445.

Example 19{[(Aminocyclopentyl)carbonylamino]cyclopentyl}-N-((S)₁-methyl-2-oxo-5-phenyl(3H-benzo[f]1,4-diazepin-3-yl))carboxamide

[1058]

[1059] The title compound was prepared in a manner similar to thatdescribed for Example 4. The product was obtained as an oil. ¹H NMR (300MHz, CD₃OD) δ7.20-7.60 (m, 9H), 5.45 (d, 1H), 3.45 (s, 3H), 2.80-2.00(m, 8H), 1.90-1.50 (m, 8H). MS [M+H]⁺445.

Example 20(2R)-2-Hydroxy-3-imidazol-2-yl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide

[1060]

[1061] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H-NMR(CDCl₃) 9.16 (d,1H), 7.69-7.52 (m, 5H), 7.33 (d, 1H), 7.24-7.15 (m, 3H), 5.45 (d, 1H),3.42 (s, 3H), 2.24-2.14 (m, 3H), 2.11-1.84 (m, 1H), 1.83-1.72 (m, 4H),1.66-1.56 (m, 2H); MS [M+H]⁺583.

Example 212-Ethoxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide

[1062]

[1063] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H-NMR(CDCl₃) 8.17 (d,1H), 7.76-7.60 (m, 5H), 7.40 (d, 1H), 7.32-7.23 (m, 1H), 6.99 (s, 1H),5.52 (d, 1H), 4.01 (d, 2H), 3.67-3.60 (q, 2H), 3.48 (s, 3H), 2.48-2.40(m, 2H), 2.14-2.08 (m, 2H), 1.89-1.83 (m, 3H), 1.64 (s, 2H), 1.29 (s,3H); MS [M+H]⁺531.

Example 223-Cyclopentyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide

[1064]

[1065] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H-NMR(CDCl₃) 8.00 (d,1H), 7.68-7.51 (m, 5H), 7.32 (d, 1H), 7.23-7.17 (m, 2H), 5.85 (s, 1H),5.41 (d, 1H), 3.39 (s, 3H), 2.42-2.22 (m, 2H), 2.20 (t, 2H), 2.10-1.90(m, 2H), 1.76-1.44 (m, 13H), 1.10-1.0 (m, 2H); MS [M +H]⁺569.

Example 23(2S)-2-Hydroxy-3-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]butanamide

[1066]

[1067] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H-NMR(CDCl₃) 8.50 (d,1H), 7.76-7.61 (m, 4H), 7.41 (d, 1H), 7.32-7.28 (m, 1H), 7.03 (s, 1H),5.53-5.51 (m, 1H),4.06 (d, 1H), 3.48 (s, 3H), 2.57-2.35 (m, 2H),2.30-2.10 (m, 2H), 2.09-1.90 (m, 1H), 1.80-1.70 (m, 5H), 1.05 (d, 3H),0.94 (d, 3H); MS [M+H]⁺545.

Example 24(2S)-2-Cyclohexyl-2-hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide

[1068]

[1069] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H-NMR(CDCl₃) 8.04(d,1H), 7.67-7.51 (m, 4H), 7.31 (d, 1H), 7.23-7.18 (m, 1H), 7.02 (s,1H), 5.42 (d, 1H), 3.94 (m, 1H), 3.78 (s, 3H), 2.42-2.25 (m, 2H),2.18-1.90 (m, 2H), 1.80-1.65 (m, 9H), 1.30-1.00 (m, 6H); MS [M +H]⁺585.

Example 25(2R)-2-Cyclohexyl-2-hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide

[1070]

[1071] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H-NMR(CDCl₃) 8.17 (d,1H), 7.67-7.52 (m, 4H), 7.32 (d, 1H), 7.23-7.15 (m, 1H), 6.89 (s, 1H),5.45 (d, 1H), 3.92 (d, 1H), 3.39 (s, 3H), 2.45-2.25 (m, 2H), 2.10-1.95(m, 2H), 1.80-1.50 (m, 10H), 1.25-1.00 (m, 6H); MS [M +H]⁺585.

Example 26(2S)-2-Amino-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide

[1072]

[1073] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H-NMR(CDCl₃) 8.95 (s,1H), 7.79-7.63 (m, 5H), 7.40-7.30 (m, 2H), 5.46 (s, 1H), 4.20 (d, 2H),4.0-3.90 (m, 1H), 3.51 (s, 3H), 2.40-2.20 (m,2H), 2.10 2.00 (m, 2H),1.90-1.70 (m, 4H), 1.40-1.20 (m, 2H), 1.10-1.00 (m, 3H), 1.00-0.90 (m,3H); MS [M+H]⁺559.

Example 27[(Cyclohexylcarbonylamino)cyclopentyl]-N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carboxamide

[1074]

[1075] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H-NMR(CDCl₃) 8.10 (d,1H), 7.75-7.62 (m, 3H), 7.42-7.39 (m, 3H), 7.30-7.20 (m, 1H), 6.11 (s,1H), 5.47 (d, 1H), 3.46 (s, 3H), 2.50-2.45 (m, 2H), 2.30-2.10 (m, 1H),2.09-1.75 (m, 9H), 1.70-1.60 (m, 1H), 1.50-1.40 (m, 2H), 1.39-1.20 (m,3H); MS [M+H]⁺555.

Example 29{[N-(3-Methylbutyl)carbamoyl]cyclopentyl}-N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carboxamide

[1076]

[1077] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.78-7.60 (m, 5H), 7.48-7.22 (m, 3H), 5.47 (d, 1H), 3.49 (s, 3H), 3.30(m, 2H), 2.38-2.22 (m, 4H), 1.84-1.38 (m, 7H), 0.90 (d, 6H). MS[M+H]⁺543.

Example 304-Methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide

[1078]

[1079] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.78-7.56 (m, 5H), 7.42-7.20 (m, 3H), 5.46 (d, 1H), 3.44(s, 3H),2.48-2.20 (m, 4H), 2.05 (m, 2H), 1.80 (m, 4H), 1.58 (m, 3H), 0.88 (d,6H). MS [M+H]⁺543.

Example 31(2S)-2-Hydroxy-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide

[1080]

[1081] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.78-7.58 (m, 5H), 7.43-7.20 (m, 3H), 5.49 (d, 1H), 4.17 (m, 1H), 3.45(s, 3H), 2.40 (m, 2H), 2.10 (m, 2H), 1.92-1.50 (m, 8H), 0.92 (m, 6H). MS[M+H]⁺559.

Example 323-Methoxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide

[1082]

[1083] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.78-7.56 (m, 5H), 7.40-7.20 (m, 3H), 5.51 (d, 1H), 3.72 (m, 2H), 3.44(s, 3H), 3.39 (s, 3H), 2.58-2.30 (m, 4H), 2.02 (m, 2H), 1.88 (m, 4H). MS[M+H]+531.

Example 33(2S)-2-Hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-3-phenylpropanamide

[1084]

[1085] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.72-7.57 (m, 5H), 7.40-7.20 (m, 3H), 5.48 (d, 1H), 4.37 (m, 1H), 3.42(s, 3H), 3.20 (q, 1H), 2.97 (q, 1H), 2.38 (m, 2H), 1.96 (m, 2H),1.80-1.52 (m, 4H). MS [M+H]⁺593.

Example 34N-[(N-{1-Methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-2-(phenylmethoxy)acetamide

[1086]

[1087] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino benzodiazepine employed inExample 1. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.74-7.55 (m, 5H), 7.40-7.20 (m, 3H), 5.48 (d, 1H), 4.61 (q, 2H), 4.12(q, 2H), 3.44 (s, 3H), 2.42 (m, 2H), 2.05 (m, 2H), 1.80 (m, 4H). MS[M+H]⁺593.

Example 35(2S)-2-Hydroxy-3-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-butanamide

[1088]

[1089] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino bisbenzazepine employed inExample 10. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.64-7.35 (m, 8H), 5.25 (d, 1H), 4.06 (d, 1H), 3.35 (s, 3H), 2.42-2.05(m, 6H), 1.80 (m, 4H), 1.05 (d, 3H), 0.95 (d, 3H). MS [M+H]⁺450.

Example 36(2S)-2-Hydroxy-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide

[1090]

[1091] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino bisbenzazepine employed inExample 10. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.64-7.32 (m, 8H), 5.24 (d, 1H), 4.20 (q, 1H), 3.34 (s, 3H), 2.38 (m,2H), 2.20-1.60 (m, 9H), 0.97 (m, 6H). MS [M+H]⁺464.

Example 373-Cyclopentyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}propanamide

[1092]

[1093] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino bisbenzazepine employed inExample 10. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.64-7.35 (m, 8H), 5.25 (d, 1H), 3.36 (s, 3H), 2.42-1.45 (m, 21H). MS[M+H]⁺474.

Example 38(2S)-2-Cyclohexyl-2-hydroxy-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-acetamide

[1094]

[1095] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino bisbenzazepine employed inExample 10. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.62-7.36 (m, 8H), 5.24 (d, 1H), 3.98 (d, 1H), 3.33 (s, 3H), 2.42-1.04(m, 19 H). MS [M+H]⁺490.

Example 393-Cyclopropyl-N-{[N-((S)-5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-propanamide

[1096]

[1097] The title compound was prepared in a manner similar to thatdescribed for Example 4. The product was obtained as an oil. ¹H NMR (300MHz CDCl₃) 7.56-7.24 (m, 8H), 5.16 (d, 1H), 3.27 (s, 3H), 2.38-2.15 (m,4H), 2.10-1.82 (m, 2H), 1.78-1.42 (m, 6H), 0.64 (m, 1H), 0.36 (m, 2H),0.02 (m, 2H). MS [M+H]⁺446.

Example 40N-{[N-(1-Butyl-5-cyclopentyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}-4-methylpentanamide

[1098]

[1099] The amino benzodiazepine core was made in a manner similar tothat described in the Scheme 6. The title compound was prepared in amanner similar to that described for Example 4. The product was obtainedas an oil. ¹H NMR (300 MHz CDCl₃) 7.60-7.22 (m, 4H), 5.25 (d, 1H), 4.36(m, 1H), 3.56 (m, 1H), 3.31 (m, 1H), 2.40-0.78 (m, 34H). MS [M+H]⁺509.

Example 41N-{[N-(5-Cyclopentyl-1-methyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}-4-methylpentanamide

[1100]

[1101] The amino benzodiazepine core was made in a manner similar tothat described in the Scheme 6. The title compound was prepared in amanner similar to that described for Example 4. The product was obtainedas an oil. ¹H NMR (300 MHz CDCl₃) 7.58-7.20 (m, 4H), 5.30 (d, 1H), 3.38(s, 3H), 3.30 (m, 1H), 2.40-1.20 (m, 21H), 0.89 (d, 6H). MS [M+H]⁺467.

Example 42(2S)-2-Hydroxy-3-methyl-N-({N-[2-oxo-1-benzyl(3H,4H,5H-benzo[f]azaperhydroepin-3-yl)]carbamoyl}cyclopentyl)butanamide

[1102]

[1103] The amino benzoazepine core was made in a manner similar to thatdescribed in J. Med. Chem. 1999, 42, 2621. The title compound wasprepared in a manner similar to that described for Example 4. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.34-7.10 (m,9H), 5.16 (m, 1H), 4.76 (m, 1H), 4.42 (m, 1H), 3.94 (m, 1H), 2.64-1.64(m, 13H), 1.00-0.86 (m, 6H). MS [M+H]⁺478.

Example 43(2S)-4-Methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-2-[(propylsulfonyl)amino]pentanamide

[1104]

[1105] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino bisbenzazepine employed inExample 10. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.62-7.32 (m, 8H), 5.40 (d, 1H), 5.24 (d, 1H), 4.02 (m, 1H), 3.34 (s,3H), 2.98 (m, 2H), 2.42-1.58 (m, 13H), 0.94-0.85 (m, 9H). MS [M+H]⁺569.

Example 44(2S)-2-Amino-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide

[1106]

[1107] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino bisbenzazepine employed inExample 10. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.60-7.30 (m, 8H), 5.22 (d, 1H), 3.32 (s, 3H), 3.08 (m, 1H), 2.48 (s,3H), 2.46-1.45 (m, 11H), 0.98-0.92 (q, 6H). MS [M+H]⁺477.

Example 452,2-Difluoro-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-pentanamide

[1108]

[1109] The title compound was prepared in a manner similar to thatdescribed for Example 4 using the amino bisbenzazepine employed inExample 10. The product was obtained as an oil. ¹H NMR (300 MHz CDCl₃)7.62-7.30 (m, 8H), 5.23 (d, 1H), 3.34 (s, 3H), 2.42-1.80 (m, 11H), 1.00(d, 6H). MS [M+H]⁺484.

Example 564-Methyl-N-{[N-(6-oxo(5H,7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide

[1110]

[1111] The title compound was prepared in a manner similar to thatdescribed for Example 4. The product was obtained as an oil. ¹H NMR (300MHz, CD₃OD) δ7.91 (d, J=6.7 Hz, 1 H), 7.63 (m, 1 H), 7.51-7.28 (m, 7 H),7.08 (d, J=7.0 Hz, 1 H), 5.84 (s, 1 H), 5.25 (d, J=6.7 Hz, 1 H),2.41-0.89 (m, 19 H); ESI MS m/z=434 [C₂₆H₃₁N₃O₃+H]⁺.

Example 57N-({N-[5-(3,3-Dimethyl-2-oxobutyl)-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide

[1112]

[1113] To a solution of4-methyl-N-{[N-(6-oxo(5H,7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide(540 mg, 1.3 mmol), in DMF (25 mL) was added K₂CO₃ (0.52 g, 3.7 mmol)and bromopinacolone (0.45 g, 2.5 mmol), and the solution was allowed tostir for 40 h at room temperature. The contents of the flask werepartitioned between EtOAc and a 5% LiCl solution (150 mL each), theorganic phase washed with 5% LiCl (2×50 mL), dried over anhydrous Na₂SO₄and concentrated to yield a white solid. This was further purified bycolumn chromatography [silica gel, EtOAc/hexanes (35:65)] to yield thetitle compound (340 mg, 51%) as a white solid. The title compound wereseparated by chiral HPLC using the following conditions: Column,Chiralpak AD column (5 cm×50 cm); Eluent, 96:4 Hexanes/2-Propanol; Flowrate, 100 mL/min; Monitoring wavelength, 220 nm.

[1114] Enantiomer A: 158 mg: mp 126-130° C.; ¹H NMR (300 MHz, CDCl₃)δ7.89 (d, J=6.7 Hz, 1 H), 7.62-7.13 (m, 8 H), 5.82 (s, 1 H), 5.35 (d,J=7.4 Hz, 1 H), 4.62 (q_(ab), J=14.1 Hz, 2 H), 2.47-1.59 (m, 13 H), 1.22(s, 9 H), 0.92 (d, J=5.8 Hz, 6 H); IR (KBr) 3410, 2958, 2475, 1724, 1663cm⁻¹; ESI MS m/z=532 [C₃₂H₄₁N₃O₄+H]⁺; HPLC 97.8%, t_(r)=24.83 min. (HPLCConditions A).

[1115] Enantiomer B: 165 mg; mp 126-130° C.; ¹H NMR (300 MHz, CDCl₃)δ7.89 (d, J=6.7 Hz, 1 H), 7.62-7.13 (m, 8 H), 5.82 (s, 1 H), 5.35 (d,J=7.4 Hz, 1 H), 4.62 (q_(ab), J=14.1 Hz, 2 H), 2.47-1.59 (m, 13 H), 1.22(s, 9 H), 0.92 (d, J=5.8 Hz, 6 H); IR (KBr) 3410, 2958, 2475, 1724, 1663cm⁻¹; ESI MS m/z=532 [C₃₂H₄₁N₃₀ ₄+H]⁺; HPLC 97.8%, t_(r)=24.83 min.(HPLC Conditions A).

Example 584-Methyl-N-[(N-{6-oxo-5-[(3-phenoxyphenyl)methyl](7H-dibenzo[d,f]azaperhydroepin-7-yl)}carbamoyl)cyclopentyl]pentanamide

[1116]

[1117] The title compound was prepared in a manner similar to thatdescribed for Example 57. The product was obtained as a white solid: mp94-100° C; ¹H NMR (500 MHz, CDCl₃) δ7.99 (d, J=6.9 Hz, 1 H), 7.58-6.43(m, 17 H), 5.82 (s, 1 H), 5.39 (d, J=7.4 Hz, 1 H), 5.12 (q_(ab), J=14.5Hz, 2 H), 2.47-1.57 (m, 13 H), 0.82 (d, J=6.1 Hz, 6 H); IR (KBr) 3332,2955, 1660, 1584, 1487 cm⁻¹; ESI MS m/z=616 [C₃₉H₄₁N₃O₄+H]⁺; HPLC 99.4%,t_(r)=19.54 min. (HPLC Conditions A).

Example 59N-{[N-(5-Butyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-4-methylpentanamide

[1118]

[1119] The title compound was prepared in a manner similar to thatdescribed for Example 57. The product was obtained as a white solid. Theenantiomers were separated by chiral HPLC using the followingconditions: Column, Chiralcel OD column (5 cm×50 cm); Eluent, 95:5Hexanes/2-Propanol; Flow rate, 100 mL/min; Monitoring wavelength, 270nm.

[1120] Enantiomer A: 197 mg: mp 123-126° C.; ¹H NMR (500 MHz, CDCl₃)δ7.99 (d, J=7.0 Hz, 1 H), 7.58-6.43 (m, 8 H), 5.91 (s, 1 H), 5.26 (d,J=7.4 Hz, 1 H), 4.29 (m, 2 H), 3.52 (m, 2 H), 2.43-1.19 (m, 15 H), 0.95(d, J=6.1 Hz, 6 H), 0.62 (m, 3 H); IR (KBr) 3325, 2957, 2871, 1655, 1498cm⁻¹; ESI MS m/z=490 [C₃₀H₃₉N₃O₃+H]⁺; HPLC 100%, t_(r)=20.25 min. (HPLCConditions A).

[1121] Enantiomer B: 167 mg: mp 110-115° C.; ¹H NMR (500 MHz, CDCl₃)δ7.99 (d, J=7.0 Hz, 1 H), 7.58-6.43 (m, 8 H), 5.91 (s, 1 H), 5.26 (d,J=7.4 Hz, 1 H), 4.29 (m, 2 H), 3.52 (m, 2 H), 2.43-1.19 (m, 15 H), 0.95(d, J=6.1 Hz, 6 H), 0.62 (m, 3 H); IR (KBr) 3325, 2957, 2871, 1655, 1498cm⁻¹; ESI MS m/z=490 [C₃₀H₃₉N₃O₃+H]⁺; HPLC 100%, t_(r)=20.26 min. (HPLCConditions A).

Example 604-Methyl-N-({N-[6-oxo-5-benzyl(7H-dibenzo[d,f]azaperhydroepin-7-yl)]carbamoyl}cyclopentyl)pentanamide

[1122]

[1123] The title compound was prepared in a manner similar to thatdescribed for Example 57. The product was obtained as a white solid: mp103-106° C.; ¹H NMR (500 MHz, CDCl₃) δ8.01 (d, J=6.8 Hz, 1 H), 7.52-7.25(m, 8 H), 7.05 (m, 3 H), 6.78 (m, 2 H), 5.84 (s, 1 H), 5.36 (d, J=7.4Hz, 1 H), 5.04 (q_(ab), J=14.7 Hz, 2 H), 2.41-1.26 (m, 13 H), 0.91 (d,J=5.8 Hz, 6 H); IR (KBr) 3325, 2956, 1655, 1498, 1396 cm⁻¹; ESI MSm/z=524 [C₃₃H₃₇N₃O₃+H]⁺; HPLC 100%, t_(r)=27.04 min. (HPLC ConditionsA).

Example 61N-({N-[5-(tert-Butyl)-1-methyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide

[1124]

[1125] c) Preparation of 25

[1126] To a stirred solution of 23 (see Scheme 6) (1.0 equiv) in CH₂Cl₂(0.1 M) was added a 30% solution of HBr in acetic acid (16 equiv). Themixture was stirred for 14 h. The reaction mixture was concentrated invacuo and dissolved in EtOAc and water and separated. The aqueous layerwas made basic using 6 N NaOH and was extracted with CH₂Cl₂. The organicextracts were washed with brine, dried over Na₂SO₄, filtered andconcentrated. The resulting solid was dissolved in CH₂Cl₂ and added to astirring solution of the acid 24 (1.2 equiv), EDC-HCl (1.5 equiv), HOBt(1.5 equiv), and DIPEA (5.0 equiv) in CH₂Cl₂ (0.15 M). The reaction wasstirred overnight, quenched with water, washed with 20% citric acid(3×), sat NaHCO₃ (2×), brine, dried over Na₂SO₄, filtered andconcentrated. Crude material was recrystallized from EtOAc and Et₂O togive 25 (4.4 g, 95%) as a white powder: ¹H NMR (500 MHz, CDCl₃)δ7.71-6.98 (m, 6 H), 5.87 (s, 1 H), 5.29 (d, 1 H), 2.38 (m, 2 H), 2.21(t, 2 H) 2.01 (m, 2 H), 1.52 (m, 7 H), 1.23 (s, 9 H), 0.88 (d, 6 H).

[1127] d) Preparation of Example 61

[1128] To a suspension of 25 (1 equiv) and freshly powdered K₂CO₃ (3.0equiv) in DMF (0.05 M) was added methyl iodide (1.5 equiv). The mixturewas stirred (5 h). To the reaction was added EtOAc and water and thelayers separated. The organic layer was washed with 5% LiCl (2×), brine,dried over Na₂SO₄, filtered and concentrated. The resulting material wasdissolved in Et₂O and concentrated in vacuo providingN-({N-[5-(tert-butyl)-1-methyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}-cyclopentyl)-4-methylpentanamide(60 mg, 66%) as a white powder: mp 175-178° C; ¹H NMR (500 MHz, CDCl₃)δ7.71-7.17 (m, 5 H), 5.89 (s, 1 H), 5.23 (d, 1 H), 3.34 (s, 3 H),2.41-2.29 (m, 3 H), 2.21 (m, 2 H), 2.04 (m, 3 H), 1.80 (m, 4 H), 1.60(m, 1 H), 1.18 (s, 9 H), 0.90 (d, 6 H); ESI MS m/z=455 [C ₂₆H₃₈N₄O₃+H]⁺;IR (KBr) 3324, 2958, 1677, 1508, 1366, 1197 cm⁻¹; HPLC 96.8%,t_(r)=15.75 min. (HPLC Conditions A).

Example 62N-({N-[5-(tert-Butyl)-1-butyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide

[1129]

[1130] The title compound was prepared in a manner similar to thatdescribed for Example 62. The product was obtained as a white powder(450 mg, 70%): mp 175-177° C.; ¹H NMR (500 MHz, CDCl₃) δ7.71-7.13 (m, 5H), 5.89 (s, 1 H), 5.20 (d, 1 H), 4.36 (m, 1 H), 3.50 (m, 1 H), 2.32 (m,3 H) 2.20 (m, 2 H), 2.02 (m, 3 H), 1.80 (m, 4 H), 1.57 (m, 1 H), 1.35(m, 2 H) 1.26 (s, 9 H), 1.21 (m, 2 H), 0.89 (d, 6 H), 0.83 (t, 3 H); ESIMS m/z=497 [C₂₉H₄₄N₄O₃+H]⁺; IR (KBr)=3321, 2959, 2363, 1676, 1508, 1365cm⁻¹; HPLC 95.4%, t_(r)=19.69 min. (HPLC Conditions A).

Example 63N-({N-[5-Butyl-2-oxo-1-(2-pyridylmethyl)(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide

[1131]

[1132] The title compound was prepared in a manner similar to thatdescribed for Example 62. The product was obtained as a white powder: mp63-67° C; ¹H NMR (CDCl₃) δ8.46-7.11 (m, 8 H), 5.89 (s, 1 H), 5.40 (d,J=6.87 Hz, 1 H), 5.28 (d, J=15.77 Hz, 1 H), 5.12 (d, J=15.82 Hz, 1 H),2.74 (m, 2 H), 2.43-0.77 (m, 27 H); ESI MS m/z=532 [C₃₁H₄₁N₅O₃+H]⁺; IR(KBr) 3310 (br.), 1670 cm⁻¹; HPLC >95% % t_(r)=17.07 min. (HPLCConditions A). Anal. Calcd for [C₃₁H₄₁N₅O₃.0.5H₂O]: C, 68.86; H, 7.83;N, 12.95. Found: C, 68.73; H, 7.86; N, 12.79.

[1133] Tables 1-4 below provide representative Examples of the compoundsof Formula (I) of the present invention. TABLE 1

Ex.# R³ L C -WXYZ R¹¹  2 3-Me-butyl NHC(═O) cyclopentyl Me phenyl  3n-butyl NHC(═O) cyclopentyl Me phenyl  4 3,5-diF-benzyl C(═O)NHcyclohexyl Me phenyl  5 3,5-diF-benzyl C(═O)NH cyclopentyl Me phenyl  63,5-diF-benzyl C(═O)NH cyclopropyl Me phenyl  7 cyclopentyl C(═O)NHcyclohexyl Me phenyl ethyl  8 3,5-diF-benzyl C(═O)NH 4-piperidyl Mephenyl  9 3,5-diF-benzyl C(═O)NH N- Me phenyl benzyloxy- carbonyl-4-piperidyl 11 benzyl O—C(═O)NH cyclopentyl Me 4-CF₃-phenyl 143-phenyl-1,1- C(═O)NH cyclopentyl Me 4-CF₃-phenyl diF-propyl 15 2-(4-C(═O)NH cyclopentyl Me 4-CF₃-phenyl piperidyl) ethyl 16 1-hydroxy-3-C(═O)NH cyclopentyl Me 4-CF₃-phenyl Me-butyl 17 2-cyclopropyl- C(═O)NHcyclopentyl Me 4-CF₃-phenyl ethyl 19 1-amino C(═O)NH cyclopentyl Mephenyl cyclopentyl 20 1-hydroxy-2- C(═O)NH cyclopentyl Me 4-CF₃-phenylimidazol-2-yl- ethyl 21 ethyoxy-methyl C(═O)NH cyclopentyl Me4-CF₃-phenyl 22 2-cyclopentyl- C(═O)NH cyclopentyl Me 4-CF₃-phenyl ethyl23 1-hydroxy-2- C(═O)NH cyclopentyl Me 4-CF₃-phenyl Me-propyl 24*1-hydroxy-1- C(═O)NH cyclopentyl Me 4-CF₃-phenyl cyclohexyl- methyl 25*1-hydroxy-1- C(═O)NH cyclopentyl Me 4-CF₃-phenyl cyclohexyl- methyl 261-NH₂-3-Me- C(═O)NH cyclopentyl Me 4-CF₃-phenyl butyl 27 cyclohexylC(═O)NH cyclopentyl Me 4-CF₃-phenyl 29 3-Me-butyl NHC(═O) cyclopentyl Me4-CF₃-phenyl 30 3-Me-butyl C(═O)NH cyclopentyl Me 4-CF₃-phenyl 311-hydroxy-3- C(═O)NH cyclopentyl Me 4-CF₃-phenyl Me-butyl 32 2-methoxy-C(═O)NH cyclopentyl Me 4-CF₃-phenyl ethyl 33 1-hydroxy-2- C(═O)NHcyclopentyl Me 4-CF₃-phenyl phenyl-ethyl 34 benzyloxy- C(═O)NHcyclopentyl Me 4-CF₃-phenyl methyl 39 2-cyclopropyl- C(═O)NH cyclopentylMe phenyl ethyl 40 3-Me-butyl C(═O)NH cyclopentyl n-butyl cyclopentyl 413-Me-butyl C(═O)NH cyclopentyl Me cyclopentyl 61 3-Me-butyl C(═O)NHcyclopentyl Me t-butyl 62 3-Me-butyl C(═O)NH cyclopentyl n-butyl t-butyl63 3-Me-butyl C(═O)NH cyclopentyl 2- n-butyl pyridyl- methyl

[1134] TABLE 2

Ex.# R³ L C Z-Y-X-W-  1 3-Me-butyl NHC(═O) cyclopentyl Me 10 3-Me-butylC(═O)NH cyclopentyl Me 35 1-hydroxy-2-Me C(═O)NH cyclopentyl Me propyl36 1-hydroxy-3-Me C(═O)NH cyclopentyl Me butyl 37 2-cyclopentyl- C(═O)NHcyclopentyl Me ethyl 38 1-hydroxy-1- C(═O)NH cyclopentyl Me cyclohexyl-methyl 43 1-(propyl- C(═O)NH cyclopentyl Me sulfamide)-3-Me- butyl 441-(N-Me-amino)- C(═O)NH cyclopentyl Me 3-Me-butyl 45 1,1-diF-3-Me-C(═O)NH cyclopentyl Me butyl 56 3-Me-butyl C(═O)NH cyclopentyl H 573-Me-butyl C(═O)NH cyclopentyl 3,3-dimethyl-2 oxobutyl 58 3-Me-butylC(═O)NH cyclopentyl 3-phenoxy-benzyl 59 3-Me-butyl C(═O)NH cyclopentyln-butyl 60 3-Me-butyl C(═O)NH cyclopentyl benzyl

[1135] TABLE 3

Ex.# R³ L C Z-Y-X-W- 12 1-hydroxy-3-Me- C(═O)NH cyclopropyl3-(4-F-phenoxy)- butyl benzyl 13 1-hydroxy-3-Me C(═O)NH cyclopentyl3-(4-F-phenoxy)- propyl benzyl

[1136] TABLE 4

Ex.# R³ L C Z-Y-X-W- 42 1-hydroxy-2-Me C(═O)NH cyclopentyl benzyl propyl

Utility

[1137] Aβ production has been implicated in the pathology of Alzheimer'sDisease (AD). The compounds of the present invention have utility forthe prevention and treatment of AD by inhibiting Aβ production. Methodsof treatment target formation of Aβ production through the enzymesinvolved in the proteolytic processing of β amyloid precursor protein.Compounds that inhibit β or γ secretase activity, either directly orindirectly, control the production of Aβ. Such inhibition of β or γsecretases reduces production of Aβ, and is expected to reduce orprevent the neurological disorders associated with Aβ protein, such asAlzheimer's Disease.

[1138] Cellular screening methods for inhibitors of Aβ production,testing methods for the in vivo suppression of Aβ production, and assaysfor the detection of secretase activity are known in the art and havebeen disclosed in numerous publications, including J. Med. Chem. 1999,42, 3889-3898, PCT publication number WO 98/22493, EPO publicationnumber 0652009, U.S. Pat. No. 5,703,129 and U.S. Pat. No. 5,593,846; allhereby incorporated by reference.

[1139] The compounds of the present invention have utility for theprevention and treatment of disorders involving Aβ production, such ascerebrovascular disorders.

[1140] Compounds of Formula (I) are expected to possess γ-secretaseinhibitory activity. The γ-secretase inhibitory activity of the compoundof the present invention is demonstrated using assays for such activity,for example, using the assay described below. Compounds of the presentinvention have been shown to inhibit the activity of γ-secretase, asdetermined by the Aβ immunoprecipitation assay.

[1141] Compounds provided by this invention should also be useful as astandard and reagent in determining the ability of a potentialpharmaceutical to inhibit Aβ production. These would be provided incommercial kits comprising a compound of this invention.

[1142] As used herein “μg” denotes microgram, “mg” denotes milligram,“g” denotes gram, “μL” denotes microliter, “mL” denotes milliliter, “L”denotes liter, “nM” denotes nanomolar, “μM” denotes micromolar, “mM”denotes millimolar, “M” denotes molar, “n” denotes nanometer, “SDS”denotes sodium dodecyl sulfate, and “DMSO” denotes dimethyl sulfoxide,and “EDTA” denotes ethylenediaminetetraacetic acid.

[1143] A compound is considered to be active if it has an IC₅₀ or K_(i)value of less than about 100 μM for the inhibition of Aβ production.Preferrably the IC₅₀ or K_(i) value is less than about 10 μM; morepreferrably the IC₅₀ or K_(i) value is less than about 0.1 μM. Thepresent invention has been shown to inhibit Aβ protein production withan IC₅₀ or K_(i) value of less than 100 μM.

[1144] β amyloid precursor protein accumulation assay

[1145] A novel assay to evaluate the accumulation of Aβ protein wasdeveloped to detect potential inhibitors of secretase. The assay usesthe N 9 cell line, characterized for expression of exogenous APP byimmunoblotting and immunoprecipitation.

[1146] The effect of test compounds on the accumulation of Aβ in theconditioned medium is tested by immunoprecipitation. Briefly, N 9 cellsare grown to confluency in 6-well plates and washed twice with 1×Hank'sbuffered salt solution. The cells are starved in methionine/cysteinedeficient media for 30 min, followed by replacement with fresh deficientmedia containing 150 uCi S35 Translabel (Amersham). Test compoundsdissolved in DMSO (final concentration 1%) are added together with theaddition of radiolabel. The cells are incubated for 4 h at 37° C. in atissue culture incubator.

[1147] At the end of the incubation period, the conditioned medium isharvested and pre-cleared by the addition of 5 μl normal mouse serum and50 μl of protein A Sepharose (Pharmacia), mixed by end-over-end rotationfor 30 minutes at 4° C., followed by a brief centrifugation in amicrofuge. The supernatant is then harvested and transferred to freshtubes containing 5 μg of a monoclonal antibody (clone 1101.1; directedagainst an internal peptide sequence in Aβ) and 50 μl protein ASepharose. After incubation overnight at 4° C., the samples are washedthree times with high salt washing buffer (50 mM Tris, pH 7.5, 500 mMNaCl, 5 mM EDTA, 0.5% Nonidet P-40), three times with low salt washbuffer (50 mM Tris, pH 7.5, 150 mM NaCl, 5 mM EDTA, 0.5% Nonidet P-40),and three times with 10 mM Tris, pH 7.5. The pellet after the last washis resuspended in SDS sample buffer (Laemmli, 1970) and boiled for 3minutes. The supernatant is then fractionated on either 10-20%Tris/Tricine SDS gels or on 16.5% Tris/Tricine SDS gels. The gels aredried and exposed to X-ray film or analyzed by phosphorimaging. Theresulting image is analyzed for the presence of Aβ polypeptides. Thesteady-state level of Aβ in the presence of a test compound is comparedto wells treated with DMSO (1%) alone. A typical test compound blocks Aβaccumulation in the conditioned medium, and is therefore consideredactive, with an IC₅₀ less than 100 μM.

[1148] C-Terminus β Amyloid Precursor Protein Accumulation Assay

[1149] The effect of a test compound on the accumulation of C-terminalfragments is determined by immunoprecipitation of APP and fragmentsthereof from cell lysates. N 9 cells are metabolically labeled as abovein the presence or absence of test compounds. At the end of theincubation period, the conditioned medium are harvested and cells lysedin RIPA buffer (10 mM Tris, pH 8.0 containing 1% Triton X-100, 1%deoxycholate, 0.1% SDS, 150 mM NaCl, 0.125% NaN₃). Again, lysates areprecleared with 5 ul normal rabbit serum/50 ul protein A Sepharose,followed by the addition of BC-1 antiserum (15 μl;) and 50 μl protein ASepharose for 16 hours at 4° C. The immunoprecipitates are washed asabove, bound proteins eluted by boiling in SDS sample buffer andfractionated by Tris/Tricine SDS-PAGE. After exposure to X-ray film orphosphorimager, the resulting images are analyzed for the presence ofC-terminal APP fragments. The steady-state level of C-terminal APPfragments is compared to wells treated with DMSO (1%) alone. A typicaltest compound stimulates C-terminal fragment accumulation in the celllysates, and is therefore considered active, with an IC₅₀ less than 100μM.

[1150] Aβ-Immunoprecipitation Assay

[1151] This immunoprecipitation assay is specific for γ-secretase (i.e.,proteolytic activity required to generate the C-terminal end of Aβeither by direct cleavage or generating a C-terminal extended specieswhich is subsequently further proteolyzed). N 9 cells are pulse labeledin the presence of a reported γ-secretase inhibitor (MDL 28170) for 1 h,followed by washing to remove radiolabel and MDL 28170. The media isreplaced and test compounds are added. The cells are chased forincreasing periods of times and Aβ is isolated from the conditionedmedium and C-terminal fragments from cell lysates (see above). The testcompound is characterized whether a stabilization of C-terminalfragments is observed and whether Aβ is generated from these accumulatedprecursor. A typical test compound prevents the generation of Aβ out ofaccumulated C-terminal fragments and is considered active with an IC₅₀less than 100 μM.

Dosage and Formulation

[1152] The compound of the present invention can be administered orallyusing any pharmaceutically acceptable dosage form known in the art forsuch administration. The active ingredient can be supplied in soliddosage forms such as dry powders, granules, tablets or capsules, or inliquid dosage forms, such as syrups or aqueous suspensions. The activeingredient can be administered alone, but is generally administered witha pharmaceutical carrier. A valuable treatise with respect topharmaceutical dosage forms is Remington's Pharmaceutical Sciences, MackPublishing.

[1153] The compound of the present invention can be administered in suchoral dosage forms as tablets, capsules (each of which includes sustainedrelease or timed release formulations), pills, powders, granules,elixirs, tinctures, suspensions, syrups, and emulsions. Likewise, theymay also be administered in intravenous (bolus or infusion),intraperitoneal, subcutaneous, or intramuscular form, all using dosageforms well known to those of ordinary skill in the pharmaceutical arts.An effective but non-toxic amount of the compound desired can beemployed to prevent or treat neurological disorders related to β-amyloidproduction or accumulation, such as Alzheimer's disease and Down'sSyndrome.

[1154] The compound of this invention can be administered by any meansthat produces contact of the active agent with the agent's site ofaction in the body of a host, such as a human or a mammal. The compoundcan be administered by any conventional means available for use inconjunction with pharmaceuticals, either as individual therapeuticagents or in a combination of therapeutic agents. The compound can beadministered alone, but generally administered with a pharmaceuticalcarrier selected on the basis of the chosen route of administration andstandard pharmaceutical practice.

[1155] The dosage regimen for the compound of the present inventionwill, of course, vary depending upon known factors, such as thepharmacodynamic characteristics of the particular agent and its mode androute of administration; the species, age, sex, health, medicalcondition, and weight of the recipient; the nature and extent of thesymptoms; the kind of concurrent treatment; the frequency of treatment;the route of administration, the renal and hepatic function of thepatient, and the effect desired. An ordinarily skilled physician orveterinarian can readily determine and prescribe the effective amount ofthe drug required to prevent, counter, or arrest the progress of thecondition.

[1156] Advantageously, the compounds of the present invention may beadministered in a single daily dose, or the total daily dosage may beadministered in divided doses of two, three, or four times daily.

[1157] The compound for the present invention can be administered inintranasal form via topical use of suitable intranasal vehicles, or viatransdermal routes, using those forms of transdermal skin patches wallknown to those of ordinary skill in that art. To be administered in theform of a transdermal delivery system, the dosage administration will,of course, be continuous rather than intermittent throughout the dosageregimen.

[1158] In the methods of the present invention, the compound hereindescribed in detail can form the active ingredient, and is typicallyadministered in admixture with suitable pharmaceutical diluents,excipients, or carriers (collectively referred to herein as carriermaterials) suitably selected with respect to the intended form ofadministration, that is, oral tablets, capsules, elixirs, syrups and thelike, and consistent with conventional pharmaceutical practices.

[1159] For instance, for oral administration in the form of a tablet orcapsule, the active drug component can be combined with an oral,non-toxic, pharmaceutically acceptable, inert carrier such as lactose,starch, sucrose, glucose, methyl callulose, magnesium stearate,dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like;for oral administration in liquid form, the oral drug components can becombined with any oral, non-toxic, pharmaceutically acceptable inertcarrier such as ethanol, glycerol, water, and the like. Moreover, whendesired or necessary, suitable binders, lubricants, disintegratingagents, and coloring agents can also be incorporated into the mixture.Suitable binders include starch, gelatin, natural sugars such as glucoseor β-lactose, corn sweeteners, natural and synthetic gums such asacacia, tragacanth, or sodium alginate, carboxymethylcellulose,polyethylene glycol, waxes, and the like. Lubricants used in thesedosage forms include sodium oleate, sodium stearate, magnesium stearate,sodium benzoate, sodium acetate, sodium chloride, and the like.Disintegrators include, without limitation, starch, methyl cellulose,agar, bentonite, xanthan gum, and the like.

[1160] The compound of the present invention can also be administered inthe form of liposome delivery systems, such as small unilamellarvesicles, large unilamallar vesicles, and multilamellar vesicles.Liposomes can be formed from a variety of phospholipids, such ascholesterol, stearylamine, or phosphatidylcholines.

[1161] Compound of the present invention may also be coupled withsoluble polymers as targetable drug carriers. Such polymers can includepolyvinylpyrrolidone, pyran copolymer,polyhydroxypropylmethacrylamide-phenol,polyhydroxyethylaspartamidephenol, or polyethyleneoxidepolylysinesubstituted with palmitoyl residues. Furthermore, the compounds of thepresent invention may be coupled to a class of biodegradable polymersuseful in achieving controlled release of a drug, for example,polylactic acid, polyglycolic acid, copolymers of polylactic andpolyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid,polyorthoesters, polyacetals, polydihydropyrans, polycyanoacylates, andcrosslinked or amphipathic block copolymers of hydrogels.

[1162] Gelatin capsules may contain the active ingredient and powderedcarriers, such as lactose, starch, cellulose derivatives, magnesiumstearate, stearic acid, and the like. Similar diluents can be used tomake compressed tablets. Both tablets and capsules can be manufacturedas sustained release products to provide for continuous release ofmedication over a period of hours. Compressed tablets can be sugarcoated or film coated to mask any unpleasant taste and protect thetablet from the atmosphere, or enteric coated for selectivedisintegration in the gastrointestinal tract.

[1163] Liquid dosage forms for oral administration can contain coloringand flavoring to increase patient acceptance. In general, water, asuitable oil, saline, aqueous dextrose (glucose), and related sugarsolutions and glycols such as propylene glycol or polyethylene glycolsare suitable carriers for parenteral solutions. Solutions for parenteraladministration preferably contain a water soluble salt of the activeingredient, suitable stabilizing agents, and if necessary, buffersubstances. Antioxidizing agents such as sodium bisulfite, sodiumsulfite, or ascorbic acid, either alone or combined, are suitablestabilizing agents. Also used are citric acid and its salts and sodiumEDTA. In addition, parenteral solutions can contain preservatives, suchas benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol.

[1164] Suitable pharmaceutical carriers are described in Remington'sPharmaceutical Sciences, Mack Publishing Company, a standard referencetext in this field.

What is claimed is:
 1. A compound of Formula (I):

or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof,wherein: L is —NR²⁶C(═O)—, —C(═O)NR²⁶—, —NR²⁶C(═O)O—, —OC(═O)NR²⁶, or—NR²⁶C(═O)NR²⁶—; R³ is —(CR⁷R^(7a))_(n)—R⁴,—(CR⁷R^(7a))_(l)—S—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—O—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—S(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—S(═O)₂—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—C(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—N(R^(7b))C(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—C(═O)N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—N(R^(7b))S(═O)₂—(CR⁷R^(7a))_(m)—R⁴, or—(CR⁷R^(7a))_(l)—S(═O)₂N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴; n is 0, 1, 2, or 3;m is 0, 1, 2, or 3; l is 1, 2, or 3; Ring C is a 3 to 8 memberedcarbocycle, wherein the carbocycle is saturated or partially saturated;optionally, the carbocycle contains a heteroatom selected from —O—, —S—,—S(═O)—, —S(═O)₂—, and —N(R²⁰)—; and wherein the carbocycle issubstituted with 0-4 R²¹; R⁴ is H, OH, OR^(14a), C₁-C₈ alkyl substitutedwith 0-3 R^(4a), C₂-C₈ alkenyl substituted with 0-3 R^(4a), C₂-C₈alkynyl substituted with 0-3 R^(4a), C₃-C₁₀ carbocycle substituted with0-3 R^(4b), C₆-C₁₀ aryl substituted with 0-3 R^(4b), or 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(4b); R^(4a), at each occurrence, isindependently selected from H, OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₁₀carbocycle substituted with 0-3 R^(4b), C₆-C₁₀ aryl substituted with 0-3R^(4b), and 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(4b); R^(4b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R⁶ isH; C₁-C₆ alkyl substituted with 0-3 R^(6a); C₃-C₁₀ carbocyclesubstituted with 0-3 R^(6b); or C₆-C₁₀ aryl substituted with 0-3 R^(6b);R^(6a), at each occurrence, is independently selected from H, C₁-C₆alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, aryl and CF₃; R^(6b),at each occurrence, is independently selected from H, OH, Cl, F, Br, I,CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, andC₁-C₄ haloalkoxy; R⁷, at each occurrence, is independently selected fromH, OH, Cl, F, Br, I, CN, NO₂, CF₃, C₁-C₄ alkyl, phenyl substituted with0-5 R^(7c); R^(7a), at each occurrence, is independently selected fromH, Cl, F, Br, I, CN, CF₃, and C₁-C₄ alkyl; R^(7b) is independentlyselected from H and C₁-C₄ alkyl; R^(7c), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, CF₃, C₁-C₄ alkoxy,and C₁-C₄ alkyl; B is a 5 to 10 membered lactam, wherein the lactam issaturated, partially saturated or unsaturated; wherein each additionallactam carbon is substituted with 0-2 R¹¹; and, optionally, the lactamcontains an additional heteroatom selected from —O—, —S—, —S(═O)—,—S(═O)₂—, —N═, —NH—, and —N(R¹⁰)—; R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷,C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, S(═O)₂R¹⁷; C₁-C₆ alkyl optionallysubstituted with 0-3 R^(10a); C₆-C₁₀ aryl substituted with 0-4 R^(10b);C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(10b); R^(10a), at each occurrence, isindependently selected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN,NO₂, NR¹⁵R¹⁶, CF₃, aryl substituted with 0-4 R^(10b); C₃-C₁₀ carbocyclesubstituted with 0-3 R^(10b), and 5 to 10 membered heterocyclecontaining 1 to 4 heteroatoms selected from nitrogen, oxygen, andsulphur, wherein said 5 to 10 membered heterocycle is substituted with0-3 R^(10b); R^(10b), at each occurrence, is independently selected fromH, OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹¹, at eachoccurrence, is independently selected from H, C₁-C₄ alkoxy, Cl, F, Br,I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹,S(═O)₂NR¹⁸R¹⁹, CF₃; C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);C₆-C₁₀ aryl substituted with 0-3 R^(11b); C₃-C₁₀ carbocycle substitutedwith 0-3 R^(11b); and 5 to 10 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 10 membered heterocycle is substituted with 0-3 R^(11b); R^(11a), ateach occurrence, is independently selected from H, C₁-C₆ alkyl, OR¹⁴,Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃; phenyl substituted with 0-3R^(11b); C₃-C₆ cycloalkyl substituted with 0-3 R^(11b); and 5 to 6membered heterocycle containing 1 to 3 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycleis substituted with 0-3 R^(11b); R^(11b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; additionally, twoR¹¹ substituents on adjacent atoms may be combined to form a 5 to 6membered heteroaryl fused radical, wherein said 5 to 6 memberedheteroaryl fused radical comprises 1 or 2 heteroatoms selected from N,O, and S; wherein said 5 to 6 membered heteroaryl fused radical issubstituted with 0-3 R¹³; additionally, two R¹¹ substituents on the sameor adjacent carbon atoms may be combined to form a C₃-C₆ carbocyclesubstituted with 0-3 R¹³; additionally, two R¹¹ substituents on adjacentatoms may be combined to form a benzo fused radical; wherein said benzofused radical is substituted with 0-4 R¹³; W is —(CR⁸R^(8a))_(p)—; p is0, 1, 2, 3, or 4; R⁸ and R^(8a), at each occurrence, are independentlyselected from H, F, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl and C₃-C₈cycloalkyl; X is a bond; C₆-C₁₀ aryl substituted with 0-3 R^(Xb); C₃-C₁₀carbocycle substituted with 0-3 R^(Xb); or 5 to 10 membered heterocyclesubstituted with 0-2 R^(Xb); R^(Xb), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ halothioalkoxy; Y is a bond or—(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—; t is 0, 1, 2, or 3; u is 0, 1, 2,or 3; R⁹ and R^(9a), at each occurrence, are independently selected fromH, F, C₁-C₆ alkyl and C₃-C₈ cycloalkyl; V is a bond, —C(═O)—, —O—, —S—,—S(═O)—, —S(═O)₂—, —N(R¹⁹)—, —C(═O)NR^(19b)—, —NR^(19b)C(═O)—,—NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, S(═O)NR^(19b)—,—C(═O)O—, or —OC(═O)—; Z is H; C₁-C₈ alkyl substituted with 1-3 R¹²;C₂-C₄ alkenyl substituted with 1-3 R¹²; C₂-C₄ alkynyl substituted with1-3 R¹²; C₁-C₈ alkyl substituted with 0-3 R^(12a); C₂-C₄ alkenylsubstituted with 0-3 R^(12a); C₂-C₄ alkynyl substituted with 0-3R^(12a); C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocyclesubstituted with 0-4 R^(12b); or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(12b); R¹²,at each occurrence, is independently selected from C₆-C₁₀ arylsubstituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4R^(12b); and 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b); R^(12a), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—; R^(12b), at each occurrence, is independently selectedfrom H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—; R¹³, at each occurrence, is independentlyselected from H, OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, and CF₃; R¹⁴ is H, phenyl substituted with 0-4 R^(14b), benzylsubstituted with 0-4 R^(14b), C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆cycloalkyl; R^(14a) is H, C₆-C₁₀ aryl, benzyl, heterocycle, or C₁-C₄alkyl; R^(14b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—; R¹⁵, at each occurrence, is independentlyselected from H, C₁-C₆ alkyl, aryl-(C₁-C₆ alkyl)- wherein the aryl issubstituted with 0-4 R^(15b), (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—; R^(15b), at each occurrence, is independently selectedfrom H, OH, Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—; R¹⁶, at each occurrence, is independentlyselected from H, C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—,and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁷ is H, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl,aryl substituted by 0-4 R^(17a), or —CH₂-aryl substituted by 0-4R^(17a); R^(17a) is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃, S(O)CH₃, SO₂CH₃,—NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl; R¹⁸, at each occurrence, isindependently selected from H, C₁-C₆ alkyl, phenyl, benzyl, phenethyl,(C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁹, at eachoccurrence, is independently selected from H, OH, C₁-C₆ alkyl, phenyl,benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R²⁰is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, S(═O)₂R¹⁷; C₁-C₆alkyl optionally substituted with 0-2 R^(20a); C₆-C₁₀ aryl substitutedwith 0-4 R^(20b); C₃-C₁₀ carbocycle substituted with 0-3 R^(20b); or 5to 10 membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycleis substituted with 0-3 R^(20b); R^(20a), at each occurrence, isindependently selected from H, C₁-C₆ alkyl, OR¹⁴, F, ═O, CN, NO₂,NR¹⁵R¹⁶, CF₃, aryl substituted with 0-4 R^(20b), and heterocyclesubstituted with 0-4 R^(20b); R^(20b), at each occurrence, isindependently selected from H, OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br,I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—; R²¹, at each occurrence, is independently selected from H,C₁-C₄ alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃; C₁-C₆ alkyl optionally substitutedwith 0-3 R^(21a); C₆-C₁₀ aryl substituted with 0-3 R^(21b); C₃-C₁₀carbocycle substituted with 0-3 R^(21b); and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(21b); R^(21a), at each occurrence, isindependently selected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN,NO₂, NR¹⁵R¹⁶, CF₃; phenyl substituted with 0-3 R^(21b); C₃-C₆ cycloalkylsubstituted with 0-3 R^(21b); and 5 to 6 membered heterocycle containing1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 6 membered heterocycle is substituted with 0-3 R^(21b);R^(21b), at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—; additionally, two R²¹ substituents on adjacent atoms maybe combined to form a 5 to 6 membered heteroaryl fused radical, whereinsaid 5 to 6 membered heteroaryl fused radical comprises 1 or 2heteroatoms selected from N, O, and S; wherein said 5 to 6 memberedheteroaryl fused radical is substituted with 0-3 R²³; additionally, twoR²¹ substituents on the same or adjacent carbon atoms may be combined toform a C₃-C₆ carbocycle substituted with 0-3 R²³; additionally, two R²¹substituents on adjacent atoms may be combined to form a benzo fusedradical; wherein said benzo fused radical is substituted with 0-4 R²³;R²³, at each occurrence, is independently selected from H, OH, C₁-C₆alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; R²⁶ is H;C₁-C₆ alkyl substituted with 0-3 R^(26a); C₃-C₁₀ carbocycle substitutedwith 0-3 R^(26b); or C₆-C₁₀ aryl substituted with 0-3 R^(26b); R^(26a),at each occurrence, is independently selected from H, C₁-C₆ alkyl, OR¹⁴,Cl, F, Br, I, ═O , CN, NO₂, NR¹⁵R¹⁶, aryl and CF₃; and R^(26b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄haloalkoxy.
 2. A compound of claim 1, wherein: L is —NR²⁶C(═O)—,—C(═O)NR²⁶—, or —OC(═O)NR²⁶—; R³ is —(CHR⁷)_(n)—R⁴,—(CHR⁷)_(l)—N—(CR⁷R^(7a))_(m)—R⁴, or —(CHR⁷)_(l)—O—(CR⁷R^(7a))_(m)—R⁴; nis 0, 1 or 2; m is 0, 1 or 2; l is 1; Ring C is a 3 to 8 memberedcarbocycle substituted with 0-4 R²¹; optionally, the carbocycle containsa heteroatom selected from —O— and —N(R²⁰)—; R⁴ is H, OH, OR^(14a),C₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenyl substituted with0-2 R^(4a), C₂-C₆ alkynyl substituted with 0-1 R^(4a), C₃-C₆ carbocyclesubstituted with 0-3 R^(4b), C₆-C₁₀ aryl substituted with 0-3 R^(4b), or5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycleis substituted with 0-3 R^(4b); R^(4a), at each occurrence, isindependently selected from H, OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆carbocycle substituted with 0-3 R^(4b), phenyl substituted with 0-3R^(4b), and 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b); R^(4b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; R⁶ is H; R⁷, at eachoccurrence, is independently selected from H, OH, F, CF₃, methyl, andethyl; Ring B is a 7 membered lactam, wherein the lactam is saturated,partially saturated or unsaturated; wherein each additional lactamcarbon is substituted with 0-2 R¹¹; and, optionally, the lactam containsa heteroatom selected from —O—, —S—, —S(═O)—, —S(═O)₂—, —N═, —NH—, and—N(R¹⁰)—; R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,S(═O)₂R¹⁷; C₁-C₆ alkyl optionally substituted with 0-2 R^(10a); C₆-C₁₀aryl substituted with 0-4 R^(10b); C₃-C₁₀ carbocycle substituted with0-3 R^(10b); or 5 to 10 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 10 membered heterocycle is substituted with 0-3 R^(10b); R^(10a), ateach occurrence, is independently selected from H, C₁-C₆ alkyl, OR¹⁴,Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, phenyl substituted with 0-4R^(10b); and 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(10b); R^(10b), at eachoccurrence, is independently selected from H, OH, C₁-C₆ alkyl, C₁-C₄alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; R¹¹, at eachoccurrence, is independently selected from H, C₁-C₄ alkoxy, Cl, F, Br,I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹,S(═O)₂NR¹⁸R¹⁹, CF₃; C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);C₆-C₁₀ aryl substituted with 0-3 R^(11b); C₃-C₁₀ carbocycle substitutedwith 0-3 R^(11b); and 5 to 10 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 10 membered heterocycle is substituted with 0-3 R^(11b); R^(11a), ateach occurrence, is independently selected from H, C₁-C₆ alkyl, OR¹⁴,Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3R^(11b); R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄haloalkoxy; additionally, two R¹¹ substituents on adjacent atoms may becombined to form a benzo fused radical; wherein said benzo fused radicalis substituted with 0-2 R¹³; additionally, two R¹¹ substituents onadjacent atoms may be combined to form a 5 to 6 membered heteroarylfused radical, wherein said 5 to 6 membered heteroaryl fused radicalcomprises 1 or 2 heteroatoms selected from N, O, and S; wherein said 5to 6 membered heteroaryl fused radical is substituted with 0-2 R¹³;additionally, two R¹¹ substituents on the same or adjacent carbon atomsmay be combined to form a C₃-C₆ carbocycle substituted with 0-2 R¹³; Wis a bond, —CH₂—, —CH(CH₃)—, —CH₂CH₂— or —CH(CH₃)CH₂—; X is a bond;phenyl substituted with 0-2 R^(Xb); C₃-C₆ cycloalkyl substituted with0-2 R^(Xb); or 5 to 6 membered heterocycle substituted with 0-2 R^(Xb);R^(Xb), at each occurrence, is independently selected from H, OH, Cl, F,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; Y is a bond, —CH₂—V—,—V—, or —V—CH₂—; V is a bond, —C(═O)—, —O—, —S—, —S—(═O)—, —S(═O)₂—,—NH—, —N(CH₃)—, or —N(CH₂CH₃)—, Z is H; C₁-C₆ alkyl; C₂-C₄ alkenyl;C₂-C₄ alkynyl; C₁-C₃ alkyl substituted with 1-2 R¹²; C₂-C₃ alkenylsubstituted with 1-2 R¹²; C₂-C₃ alkynyl substituted with 1-2 R¹²; C₆-C₁₀aryl substituted with 0-4 R^(12b); C₃-C₆ carbocycle substituted with 0-3R^(12b); or 5 to 10 membered heterocycle substituted with 0-3 R^(12b);R¹², at each occurrence, is independently selected from C₆-C₁₀ arylsubstituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4R^(12b); and 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b); R^(12b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹³,at each occurrence, is independently selected from H, OH, C₁-C₆ alkyl,C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; R¹⁴ is H, phenyl,benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl; R^(14a) is H, phenyl, benzyl,or C₁-C₄ alkyl; R¹⁵, at each occurrence, is independently selected fromH, C₁-C₄ alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄alkyl)-S(═O)₂—; R¹⁶, at each occurrence, is independently selected fromH, OH, C₁-C₄ alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄alkyl)-S(═O)₂—; R¹⁷ is H, methyl, ethyl, propyl, butyl, methoxymethyl,ethoxymethyl, methoxyethyl, ethoxyethyl, phenyl substituted by 0-3R^(17a), or —CH₂-phenyl substituted by 0-3 R^(17a); R^(17a) is H,methyl, methoxy, —OH, F, Cl, CF₃, or OCF₃; R¹⁸, at each occurrence, isindependently selected from H, methyl, ethyl, propyl, butyl, phenyl,benzyl, and phenethyl; R¹⁹, at each occurrence, is independentlyselected from H, methyl, and ethyl; R²⁰ is H or C(═O)OR¹⁷; R²⁶ is H,methyl, or ethyl.
 3. A compound of claim 2, wherein: Ring C is selectedfrom:

 wherein Ring C is substituted with 0-2 R²¹; and Ring B is selectedfrom:


4. A compound of claim 3, wherein: L is —NHC(═O)—, —C(═O)NH—, or—OC(═O)NH—; R³ is R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴; R⁴ is C₁-C₆ alkylsubstituted with 0-3 R^(4a), C₂-C₆ alkenyl substituted with 0-1 R^(4a),or C₂-C₆ alkynyl substituted with 0-1 R^(4a); R^(4a), at eachoccurrence, is independently selected from H, OH, F, NR¹⁵R¹⁶, CF₃, C₃-C₆carbocycle substituted with 0-3 R^(4b), phenyl substituted with 0-3R^(4b), and 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b); wherein said 5 to 6membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl,furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl,pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl; R^(4b), ateach occurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶,CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, butyl,methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; W is abond, —CH₂—, —CH(CH₃)—, —CH₂CH₂— or —CH(CH₃)CH₂—; X is a bond, phenyl,C₃-C₆ cycloalkyl, or 5 to 6 membered heterocycle; Y is a bond, —C(═O)—,—O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—, or —N(CH₂CH₃)—, Z is H;C₁-C₆ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₃ alkyl substituted with1-2 R¹²; C₂-C₃ alkenyl substituted with 1-2 R¹²; C₂-C₃ alkynylsubstituted with 1-2 R¹²; C₆-C₁₀ aryl substituted with 0-4 R^(12b);C₃-C₆ carbocycle substituted with 0-3 R^(12b); or 5 to 6 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 6 membered heterocycle issubstituted with 0-3 R^(12b); wherein said 5 to 6 membered heterocycleis selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl,thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl,oxazolyl, isoxazolyl, and tetrazolyl; R¹², at each occurrence, isindependently selected from C₆-C₁₀ aryl substituted with 0-4 R^(12b);C₃-C₆ carbocycle substituted with 0-3 R^(12b); and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(12b); wherein said 5 to 6 membered heterocycleis selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl,thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl,oxazolyl, isoxazolyl, and tetrazolyl; R^(12b), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; R¹³, at each occurrence,is independently selected from H, OH, methyl, ethyl, propyl, butyl,methoxy, ethoxy, Cl, F, Br, CN, NR¹⁵R¹⁶, and CF₃; R¹⁴ is H, phenyl,benzyl, methyl, ethyl, propyl, or butyl; R¹⁵, at each occurrence, isindependently selected from H, methyl, ethyl, propyl, and butyl; R¹⁶, ateach occurrence, is independently selected from H, OH, methyl, ethyl,propyl, butyl, benzyl, phenethyl, methyl-C(═O)—, ethyl-C(═O)—,methyl-S(═O)₂—, ethyl-S(═O)₂—, and propyl-S(═O)₂—; R¹⁸, at eachoccurrence, is independently selected from H, methyl, ethyl, propyl,butyl, phenyl, benzyl, and phenethyl; R¹⁹, at each occurrence, isindependently selected from H, methyl, and ethyl; R²⁰ is H.
 5. Acompound of claim 3, wherein: L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃,—CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂, —CH(OH)CH(CH₃)₂,—CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃, —CF₂CH₂CH(CH₃)₂,—CH(NHCH₃)CH₂CH(CH₃)₂, —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl- ,cyclopentyl-, cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,1-NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,(4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,(3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,(3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,(2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,(2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,(3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,(2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,(2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,(3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,(3-F-5-Cl-phenyl)CH₂CH₂—, 4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—,phenyl-CH₂CH(OH)—, imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—; Ring C isselected from:

Ring B is selected from:

 wherein each benzo fused ring is substituted with 0-1 R¹³; W is a bondor —CH₂—; X is a bond;

Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or —N(CH₃)—, Zis phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl,4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl,2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl, 2,3-diCF-phenyl,2,4-diCF-phenyl, 2,5-diCF-phenyl, 2,6-diCl-phenyl, 3,4-diCl-phenyl,3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Cl-4-F-phenyl,2-MeO-phenyl, 3-Meo-phenyl, 4-Meo-phenyl, 2-Me-phenyl, 3-Me-phenyl,4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl, 2-CF₃O-phenyl,3-CF₃O-phenyl, 4-CF₃O-phenyl, furanyl, thienyl, pyridyl, 2-Me-pyridyl,3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl, isoxazolyl,1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,morpholino, N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,(3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—,(4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—,(4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—,4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—,(4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—,(2-Me-pyridyl)CH₂—, (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—,(1-imidazolyl)CH₂—, (oxazolyl)CH₂—, (isoxazolyl)CH₂—,(1-benzimidazolyl)CH₂—, (cyclopropyl)CH₂—, (cyclobutyl)CH₂—,(cyclopentyl)CH₂—, (cyclohexyl)CH₂—, (morpholino)CH₂—,(N-pipridinyl)CH₂—, phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—,(2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—,(2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,(2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,(3-Cl-4-F-phenyl)CH₂CH₂—, (2-MeO-phenyl)CH₂CH₂—,(3-MeO-phenyl)CH₂CH₂CH₂—(4-MeO-phenyl)CH₂CH₂—, (2-Me-phenyl)CH₂CH₂—,(3-Me-phenyl)CH₂CH₂—, (4-Me-phenyl)CH₂CH₂—, (2-MeS-phenyl)CH₂CH₂—,(3-MeS-phenyl)CH₂CH₂—, (4-MeS-phenyl)CH₂CH₂—, (2-CF₃O-phenyl)CH₂CH₂—,(3-CF₃O-phenyl)CH₂CH₂—, (4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—,(thienyl) CH₂CH₂—, (pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—,(3-Me-pyridyl)CH₂CH₂—, (4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—,(oxazolyl)CH₂CH₂—, (isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—,(cyclopropyl)CH₂CH₂—, (cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—,(cyclohexyl)CH₂CH₂—, (morpholino)CH₂CH₂—, or (N-pipridinyl)CH₂CH₂—; R¹⁰is H, methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl,(4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—, 4-Cl-phenyl, (4-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,(4-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—, or(4-CF₃-phenyl)CH₂CH₂—; R¹¹, at each occurrence, is independentlyselected from H, ═O, methyl, ethyl, phenyl, benzyl, phenethyl,4-F-phenyl, (4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—, 3-F-phenyl,(3-F-phenyl)CH₂—, (3-F-phenyl)CH₂CH₂—, 2-F-phenyl, (2-F-phenyl)CH₂—,(2-F-phenyl)CH₂CH₂—, 4-Cl-phenyl, (4-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂CH₂—, 3-Cl-phenyl, (3-Cl-phenyl)CH₂—,(3-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,(4-CH₃-phenyl)CH₂CH₂—, 3-CH₃-phenyl, (3-CH₃-phenyl)CH₂—,(3-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—,(4-CF₃-phenyl)CH₂CH₂—, cyclopentyl, pyrid-2-yl, pyrid-3-yl, andpyrid-4-yl; R¹³, at each occurrence, is independently selected from H,F, Cl, OH, —CH₃, —CH₂CH₃, —OCH₃, and —CF₃; and R²⁰ is H.
 6. A compoundof Formula (I):

or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof,wherein: L is —NR²⁶C(═O)—, —C(═O)NR²⁶—, —NR²⁶C(═O)O—, —OC(═O)NR²⁶, or—NR²⁶C(═O) NR²⁶—; R³ is —(CR⁷R^(7a))_(n)—R⁴, —(CR⁷R^(7a))_(l)—S—R⁴,—(CR⁷R^(7a))_(l)—O—R⁴; —(CR⁷R^(7a))_(l)—N(R^(7b))—R⁴,—(CR⁷R^(7a))_(l)—S(═O)—R⁴, or —(CR⁷R^(7a))_(l)—S(═O)₂—R⁴; n is 0, 1 or2; l is 1 or 2; R⁴ is H, C₁-C₈ alkyl substituted with 0-3 R^(4a), C₂-C₈alkenyl substituted with 0-3 R^(4a), C₂-C₈ alkynyl substituted with 0-3R^(4a), C₃-C₁₀ carbocycle substituted with 0-3 R^(4b), C₆-C₁₀ arylsubstituted with 0-3 R^(4b), or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(4b);R^(4a), at each occurrence, is independently selected from H, OH, F, Cl,Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),C₆-C₁₀ aryl substituted with 0-3 R^(4b), and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(4b); R^(4b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; Ring C is a 3-8membered carbocycle; wherein said 3-8 membered carbocycle is saturatedor partially unsaturated; wherein said 3-8 membered carbocycle issubstituted with 0-4 R²¹; and optionally, the carbocycle contains aheteroatom selected from —O— and —N(R²⁰)—; additionally, two R²¹substituents on adjacent atoms may be combined to form a benzo fusedradical; wherein said benzo fused radical is substituted with 0-4 R²³;additionally, two R²¹ substituents on adjacent atoms may be combined toform a 5 to 6 membered heteroaryl fused radical, wherein said 5 to 6membered heteroaryl fused radical comprises 1 or 2 heteroatoms selectedfrom N, O, and S; wherein said 5 to 6 membered heteroaryl fused radicalis substituted with 0-3 R²³; additionally, two R²¹ substituents on thesame or adjacent carbon atoms may be combined to form a C₃-C₆ carbocyclesubstituted with 0-3 R²³; R²¹, at each occurrence, is independentlyselected from H, OH, Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, NR¹⁵R¹⁶, OR^(14a), C₁-C₄ alkyl, C₂-C₆ alkenyl, alkynyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—, C₃-C₆carbocycle, phenyl, and a 5 to 6 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur; R⁶ is H,methyl, or ethyl; R⁷, at each occurrence, is independently H or C₁-C₄alkyl; R^(7a), at each occurrence, is independently H or C₁-C₄ alkyl;R^(7b) is H or C₁-C₄ alkyl; Ring B is selected from:

R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, S(═O)₂R¹⁷;C₁-C₆ alkyl optionally substituted with 0-3 R^(10a); C₆-C₁₀ arylsubstituted with 0-4 R^(10b); C₃-C₁₀ carbocycle substituted with 0-3R^(10b); or 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(10b); R^(10a), at eachoccurrence, is independently selected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F,Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or aryl substituted with 0-4 R^(10b);R^(10b), at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—; R¹¹, at each occurrence, is independently selected from H,C₁-C₄ alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃; C₁-C₆ alkyl optionally substitutedwith 0-3 R^(11a); C₆-C₁₀ aryl substituted with 0-3 R^(11b); C₃-C₁₀carbocycle substituted with 0-3 R^(11b); and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(11b); R^(11a), at each occurrence, isindependently selected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN,NO₂, NR¹⁵R¹⁶, CF₃; phenyl substituted with 0-3 R^(11b); C₃-C₆ cycloalkylsubstituted with 0-3 R^(11b); and 5 to 6 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 6 membered heterocycle is substituted with 0-3 R^(11b);R^(11b), at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—; W is a bond or —(CH₂)_(p)—; p is 1 or 2; X is a bond;phenyl substituted with 0-2 R^(Xb); C₃-C₆ carbocycle substituted with0-2 R^(Xb); or 5 to 6 membered heterocycle substituted with 0-2 R^(Xb);R^(Xb), at each occurrence, is independently selected from H, OH, Cl, F,Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, C₁-C₃ haloalkoxy, and C₁-C₃halothioalkoxy; Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—,—N(R¹⁹)—, —C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—,—S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or—OC(═O)—; Z is H; C₁-C₈ alkyl substituted with 0-3 R^(12a); C₂-C₆alkenyl substituted with 0-3 R^(12a); C₂-C₆ alkynyl substituted with 0-3R^(12a); C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocyclesubstituted with 0-4 R^(12b); or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(12b);R^(12a), at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,C₁-C₄ haloalkyl-S—, C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀carbocycle substituted with 0-4 R^(12b); and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(12b); R^(12b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹³, at eachoccurrence, is independently selected from H, OH, C₁-C₆ alkyl, C₁-C₄alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; R¹⁴ is H, phenyl,benzyl, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆ cycloalkyl; R^(14a) isH, phenyl, benzyl, or C₁-C₄ alkyl; R¹⁵, at each occurrence, isindependently selected from H, C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₆alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁶, at each occurrence, isindependently selected from H, OH, C₁-C₆ alkyl, benzyl, phenethyl,(C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁷ is H, C₁-C₆ alkyl,C₂-C₆ alkoxyalkyl, aryl substituted by 0-4 R^(17a), or —CH₂-arylsubstituted by 0-4 R^(17a); R^(17a) is H, methyl, ethyl, propyl, butyl,methoxy, ethoxy, propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃,S(O)CH₃, SO₂CH₃, —NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl; R¹⁸, at eachoccurrence, is independently selected from H, C₁-C₆ alkyl, phenyl,benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁹,at each occurrence, is independently selected from H, OH, methyl, ethyl,propyl, butyl, phenyl, benzyl, and phenethyl; R^(19b), at eachoccurrence, is independently is H or C₁-C₄ alkyl; R²⁰ is H, C₁-C₄ alkyl,or C(═O)OR¹⁷; R²³, at each occurrence, is independently selected from H,OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;and R²⁶ is H or C₁-C₄ alkyl.
 7. A compound of claim 6 of Formula (Ia):

or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof,wherein: L is —NR²⁶C(═O)—, —C(═O)NR²⁶—, —NR²⁶C(═O)O—, —OC(═O)NR²⁶, or—NR²⁶C(═O)NR²⁶—; R³ is —(CHR⁷)_(n)—R⁴, —(CHR⁷)_(l)—S—R⁴,—(CHR⁷)_(l)—O—R⁴; —(CR⁷R^(7a))_(l)—N(R^(7b))—R⁴,—(CR⁷R^(7a))_(l)—S(═O)—R⁴, or —(CR⁷R^(7a))_(l)—S(═O)₂—R⁴; n is 0, 1 or2; l is 1 or 2; R⁴ is H, C₁-C₈ alkyl substituted with 0-3 R^(4a), C₂-C₈alkenyl substituted with 0-3 R^(4a), C₂-C₈ alkynyl substituted with 0-3R^(4a), C₃-C₁₀ carbocycle substituted with 0-3 R^(4b), C₆-C₁₀ arylsubstituted with 0-3 R^(4b), or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(4b);R^(4a), at each occurrence, is independently selected from H, OH, F, Cl,Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),C₆-C₁₀ aryl substituted with 0-3 R^(4b), and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(4b); R^(4b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; Ring C is a 3-8membered carbocycle; wherein said 3-8 membered carbocycle is saturatedor partially unsaturated; wherein said 3-8 membered carbocycle issubstituted with 0-4 R²¹; optionally, the carbocycle contains aheteroatom selected from —O—, and —N(R²⁰)—; additionally, two R²¹substituents on adjacent atoms may be combined to form a benzo fusedradical; wherein said benzo fused radical is substituted with 0-4 R²³;additionally, two R²¹ substituents on the same or adjacent carbon atomsmay be combined to form a C₃-C₆ carbocycle substituted with 0-3 R²³;R²¹, at each occurrence, is independently selected from H, OH, Cl, F,Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶,OR^(14a), C₁-C₄ alkyl, C₂-C₆ alkenyl, alkynyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—, C₃-C₆ carbocycle,phenyl, and a 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur; R⁷, at each occurrence, isindependently H, methyl, or ethyl; R^(7b) is H, methyl, or ethyl; Ring Bis selected from:

R¹¹, at each occurrence, is independently selected from H, C₁-C₄ alkoxy,Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹,S(═O)₂NR¹⁸R¹⁹, CF₃; C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);C₆-C₁₀ aryl substituted with 0-3 R^(11b); C₃-C₁₀ carbocycle substitutedwith 0-3 R^(11b); and 5 to 10 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 10 membered heterocycle is substituted with 0-3 R^(11b); R^(11a), ateach occurrence, is independently selected from H, C₁-C₆ alkyl, OR¹⁴,Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃; phenyl substituted with 0-3R^(11b); C₃-C₆ cycloalkyl substituted with 0-3 R^(11b); and 5 to 6membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycleis substituted with 0-3 R^(11b); R^(11b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; W is a bond or—(CH₂)_(p)—; p is 1 or 2; X is a bond; phenyl substituted with 0-2R^(Xb); C₃-C₆ carbocycle substituted with 0-2 R^(Xb); or 5 to 6 memberedheterocycle substituted with 0-2 R^(Xb); R^(Xb), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₃haloalkyl, C₁-C₃ haloalkoxy, and C₁-C₃ halothioalkoxy; Y is a bond,—C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—, —C(═O)NR^(19b)—,—NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—,—S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—; Z is H; C₁-C₈ alkyl substitutedwith 0-3 R^(12a); C₂-C₆ alkenyl substituted with 0-3 R^(12a); C₂-C₆alkynyl substituted with 0-3 R^(12a); C₆-C₁₀ aryl substituted with 0-4R^(12b); C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or 5 to 10membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycleis substituted with 0-3 R^(12b); R^(12a), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶,—C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl,C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substitutedwith 0-4 R^(12b); and 5 to 10 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 10 membered heterocycle is substituted with 0-3 R^(12b); R^(12b), ateach occurrence, is independently selected from H, OH, Cl, F, Br, I, CN,NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹³,at each occurrence, is independently selected from H, OH, C₁-C₆ alkyl,C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; R¹⁴ is H, phenyl,benzyl, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆ cycloalkyl; R^(14a) isH, phenyl, benzyl, or C₁-C₄ alkyl; R¹⁵, at each occurrence, isindependently selected from H, C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₆alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁶, at each occurrence, isindependently selected from H, OH, C₁-C₆ alkyl, benzyl, phenethyl,(C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁷ is H, C₁-C₆ alkyl,C₂-C₆ alkoxyalkyl, aryl substituted by 0-4 R^(17a), or —CH₂-arylsubstituted by 0-4 R^(17a); R^(17a) is H, methyl, ethyl, propyl, butyl,methoxy, ethoxy, propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃,S(O)CH₃, SO₂CH₃, —NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl; R¹⁸, at eachoccurrence, is independently selected from H, C₁-C₆ alkyl, phenyl,benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁹,at each occurrence, is independently selected from H, OH, methyl, ethyl,propyl, butyl, phenyl, benzyl, phenethyl; R²⁰ is H, C₁-C₄ alkyl, orC(═O)OR¹⁷; R²³, at each occurrence, is independently selected from H,OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;and R²⁶ is H or C₁-C₄ alkyl.
 8. A compound of claim 7 of Formula (Ic):

or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof,wherein: L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; R³ is —(CH₂)_(n)—R⁴,—(CH₂)_(l)—S—R⁴, —(CH₂)_(l)—O—R⁴, or —(CH₂)_(l)—N(R^(7b))—R⁴; n is 0, 1or 2; l is 1 or 2; R⁴ is C₁-C₈ alkyl substituted with 0-3 R^(4a), C₂-C₈alkenyl substituted with 0-3 R^(4a), C₂-C₈ alkynyl substituted with 0-3R^(4a), C₃-C₁₀ carbocycle substituted with 0-3 R^(4b), C₆-C₁₀ arylsubstituted with 0-3 R^(4b), or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(4b);R^(4a), at each occurrence, is independently selected from H, OH, F, Cl,Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),C₆-C₁₀ aryl substituted with 0-3 R^(4b), and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(4b); R^(4b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R^(7b) is H,methyl, or ethyl; Ring C is a 3-8 membered carbocycle; wherein said 3-8membered carbocycle is saturated or partially unsaturated; wherein said3-8 membered carbocycle is substituted with 0-3 R²¹; optionally, thecarbocycle contains a heteroatom selected from —O—, and —N(R²⁰)—; R²¹,at each occurrence, is independently selected from H, OH, Cl, F, Br, I,CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶, OR^(14a),C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; W is a bond, —CH₂—,—CH₂CH₂—; X is a bond; phenyl substituted with 0-2 R^(Xb); C₃-C₆cycloalkyl substituted with 0-2 R^(Xb); or 5 to 6 membered heterocyclesubstituted with 0-2 R^(Xb); R^(Xb), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy; Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—,—N(R¹⁹)—, —C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—,—S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or—OC(═O)—; Z is H; C₁-C₈ alkyl substituted with 0-3 R^(12a); C₂-C₆alkenyl substituted with 0-3 R^(12a); C₂-C₆ alkynyl substituted with 0-3R^(12a); C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocyclesubstituted with 0-4 R^(12b); or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(12b);R^(12a), at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,C₁-C₄ haloalkyl-S—, C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀carbocycle substituted with 0-4 R^(12b); and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(12b); R^(12b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹³, at eachoccurrence, is independently selected from H, OH, C₁-C₆ alkyl, C₁-C₄alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; R^(14a) is H, phenyl,benzyl, or C₁-C₄ alkyl; R¹⁵, at each occurrence, is independentlyselected from H, C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—,and (C₁-C₄ alkyl)-S(═O)₂—; R¹⁶, at each occurrence, is independentlyselected from H, OH, C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₄alkyl)-C(═O)—, and (C₁-C₄ alkyl)-S(═O)₂—; and R²⁰ is H or C₁-C₄ alkyl.9. A compound of claim 8, wherein: L is —NHC(═O)—, —C(═O)NH—, or—OC(═O)NH—; R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴; R⁴ isC₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenyl substituted with0-3 R^(4a), C₂-C₆ alkynyl substituted with 0-3 R^(4a), C₃-C₆ carbocyclesubstituted with 0-3 R^(4b), phenyl substituted with 0-3 R^(4b), or 5 to6 membered heterocycle containing 1 to 3 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycleis substituted with 0-3 R^(4b); R^(4a), at each occurrence, isindependently selected from H, OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆carbocycle substituted with 0-3 R^(4b), phenyl substituted with 0-3R^(4b), and 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b); R^(4b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; RingC is a 3-6 membered carbocycle; wherein said 3-6 membered carbocycle issaturated or partially unsaturated; wherein said 3-6 membered carbocycleis substituted with 0-2 R²¹; optionally, the carbocycle contains aheteroatom selected from —O—, and —N(R²⁰)—; R²¹, at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, CF₃, acetyl,SCH₃, methyl, ethyl, methoxy, ethoxy, allyl, —OCF₃, and —SCF₃; W is abond, —CH₂—, —CH₂CH₂—; X is a bond; phenyl substituted with 0-1 R^(Xb);C₃-C₆ cycloalkyl substituted with 0-1 R^(Xb); or 5 to 6 memberedheterocycle substituted with 0-1 R^(Xb); R^(Xb) is selected from H, OH,Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl,propyl, methoxy, ethoxy, propoxy, and —OCF₃; Y is a bond, —C(═O)—, —O—,—S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—, or —N(CH₂CH₃)—; Z is H; C₁-C₈alkyl substituted with 0-3 R^(12a); C₂-C₆ alkenyl substituted with 0-3R^(12a); C₂-C₆ alkynyl substituted with 0-3 R^(12a); C₆-C₁₀ arylsubstituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4R^(12b); or 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b); R^(12a), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄haloalkyl-S—, C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀carbocycle substituted with 0-4 R^(12b); and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(12b); R^(12b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹³, at eachoccurrence, is independently selected from H, OH, C₁-C₆ alkyl, C₁-C₄alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; R¹⁵, at eachoccurrence, is independently selected from H, C₁-C₄ alkyl, and benzyl;R¹⁶, at each occurrence, is independently selected from H, OH, methyl,ethyl, propyl, butyl, benzyl, phenethyl, methyl-C(═O)—, ethyl-C(═O)—,methyl-S(═O)₂—, ethyl-S(═O)₂—, and propyl-S(═O)₂—; and R²⁰ is H or C₁-C₄alkyl.
 10. A compound of claim 9, wherein: L is —NHC(═O)—, —C(═O)NH—, or—OC(═O)NH—; R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴; R⁴ isC₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenyl substituted with0-3 R^(4a), or C₂-C₆ alkynyl substituted with 0-3 R^(4a); R^(4a), ateach occurrence, is independently selected from is H, OH, F, Cl, Br, I,NR¹⁵R¹⁶, CF₃, C₃-C₆ carbocycle substituted with 0-3 R^(4b), phenylsubstituted with 0-3 R^(4b), and 5 to 6 membered heterocycle containing1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 6 membered heterocycle is substituted with 0-3 R^(4b); whereinsaid 5 to 6 membered heterocycle is selected from pyridinyl,pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,and tetrazolyl; R^(4b), at each occurrence, is independently selectedfrom H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—; Ring C is a 3-6 membered carbocycle selectedfrom:

 wherein said 3-6 membered carbocycle is substituted with 0-1 R²¹; R²¹is selected from H, OH, Cl, F, CN, CF₃, methyl, ethyl, methoxy, ethoxy,allyl, and —OCF₃; W is a bond or —CH₂—; X is a bond, phenyl, C₃-C₆cycloalkyl or 5 to 6 membered heterocycle; Y is a bond, —C(═O)—, —O—,—S—, —S—(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—, or —N(CH₂CH₃)—; Z is H; C₁-C₈alkyl substituted with 0-3 R^(12a); C₂-C₆ alkenyl substituted with 0-3R^(12a); C₂-C₆ alkynyl substituted with 0-3 R^(12a); C₆-C₁₀ arylsubstituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4R^(12b); or 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b); R^(12a) at eachoccurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, butyl,methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; phenylsubstituted with 0-4 R^(12b); C₃-6 carbocycle substituted with 0-4R^(12b); and 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(12b); R^(12b), at eachoccurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, butyl,methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; R¹³, ateach occurrence, is independently selected from H, OH, methyl, ethyl,propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN, NR¹⁵R¹⁶, and CF₃; R¹⁵, ateach occurrence, is independently selected from H, methyl, ethyl,propyl, and butyl; and R¹⁶, at each occurrence, is independentlyselected from H, OH, methyl, ethyl, propyl, butyl, benzyl, andphenethyl; and R²⁰ is H, methyl, or ethyl.
 11. A compound of claim 10,wherein: L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; Ring C is selectedfrom:

R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃,—CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂, —CH(OH)CH(CH₃)₂,—CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃, —CF₂CH₂CH(CH₃)₂,—CH(NHCH₃)CH₂CH(CH₃)₂, —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl- ,cyclopentyl-, cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,1-NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,(4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,(3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,(3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,(2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,(2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,(3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,(2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,(2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,(3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,(3-F-5-Cl-phenyl)CH₂CH₂—, 4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—,phenyl-CH₂CH(OH)—, imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—; W is abond or —CH₂—; X is a bond;

Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or —N(CH₃)—, Zis methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl,t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl,3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl,2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl,2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl,3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl,3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl,2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl, furanyl, thienyl, pyridyl,2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl,isoxazolyl, 1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, morpholino, N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,(3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—,(4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—,(4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—,4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—,(4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—,(2-Me-pyridyl)CH₂—, (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—,(1-imidazolyl)CH₂—, (oxazolyl)CH₂—, (isoxazolyl)CH₂—,(1-benzimidazolyl)CH₂—, (cyclopropyl)CH₂—, (cyclobutyl)CH₂—,(cyclopentyl)CH₂—, (cyclohexyl)CH₂—, (morpholino)CH₂—,(N-pipridinyl)CH₂—, phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—,(2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—,(2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,(2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,(3-Cl-4-F-phenyl)CH₂CH₂—, (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—,(4-MeO-phenyl)CH₂CH₂—, (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—,(4-Me-phenyl)CH₂CH₂—, (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—,(4-MeS-phenyl)CH₂CH₂—, (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,(4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—, m(thienyl)CH₂CH₂—,(pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,(4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,(isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—,(cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—, (cyclohexyl)CH₂CH₂—,(morpholino)CH₂CH₂—, or (N-pipridinyl)CH₂CH₂—; R¹³, at each occurrence,is independently selected from H, F, Cl, OH, —CH₃, —CH₂CH₃, —OCH₃, or—CF₃. R²⁰ is H, methyl, or ethyl.
 12. A compound of claim 7 of Formula(Id) or Formula (Ie),

or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof,wherein: L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; R³ is —(CH₂)_(n)—R⁴,—(CH₂)_(l)—S—R⁴, —(CH₂)_(l)—O—R⁴, or —(CH₂)_(l)—N(R^(7b))—R⁴; n is 0, 1or 2; l is 1 or 2; R⁴ is C₁-C₈ alkyl substituted with 0-3 R^(4a), C₂-C₈alkenyl substituted with 0-3 R^(4a), C₂-C₈ alkynyl substituted with 0-3R^(4a), C₃-C₁₀ carbocycle substituted with 0-3 R^(4b), C₆-C₁₀ arylsubstituted with 0-3 R^(4b), or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(4b);R^(4a), at each occurrence, is independently selected from H, OH, F, Cl,Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),C₆-C₁₀ aryl substituted with 0-3 R^(4b), and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(4b); R^(4b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R^(7b) is H,methyl, or ethyl; Ring C is a 3-8 membered carbocycle; wherein said 3-8membered carbocyclic moiety is saturated or partially saturated; whereinsaid 3-8 membered carbocyclic moiety is substituted with 0-3 R²¹;optionally, the carbocycle contains a heteroatom selected from —O— and—N(R²⁰)—; R²¹, at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶,OR^(14a), C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹¹, at eachoccurrence, is independently selected from H, ═O, NR¹⁸R¹⁹, CF₃; C₁-C₄alkyl optionally substituted with 0-1 R^(11a); phenyl substituted with0-3 R^(11b); C₃-C₆ carbocycle substituted with 0-3 R^(11b); and 5 to 7membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycleis substituted with 0-3 R^(11b); wherein said 5 to 7 memberedheterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl,thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl,imidazolyl, oxazolyl, isoxazolyl, homopiperidinyl, and tetrazolyl;R^(11a), at each occurrence, is independently selected from H, C₁-C₄alkyl, OR¹⁴, F, Cl, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3R^(11b); R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; W is a bond, —CH₂—,—CH₂CH₂—; X is a bond; phenyl substituted with 0-2 R^(Xb); C₃-C₆cycloalkyl substituted with 0-2 R^(Xb); or 5 to 6 membered heterocyclesubstituted with 0-2 R^(Xb); R^(Xb), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy; Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—,—N(R¹⁹)—, —C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—,—S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or—OC(═O)—; Z is H; C₁-C₈ alkyl substituted with 0-3 R^(2a); C₂-C₆ alkenylsubstituted with 0-3 R^(12a); C₂-C₆ alkynyl substituted with 0-3R^(12a); C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocyclesubstituted with 0-4 R^(12b); or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(12b);R^(12a), at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,C₁-C₄ haloalkyl-S—, C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀carbocycle substituted with 0-4 R^(12b); and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(12b); R^(12b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹³, at eachoccurrence, is independently selected from H, OH, C₁-C₆ alkyl, C₁-C₄alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; R¹⁴ is H, phenyl,benzyl, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆ cycloalkyl; R^(14a) isH, phenyl, benzyl, or C₁-C₄ alkyl; R¹⁵, at each occurrence, isindependently selected from H, C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₆alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁶, at each occurrence, isindependently selected from H, OH, C₁-C₆ alkyl, benzyl, phenethyl,(C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄ alkyl)-S(═O)₂—; R¹⁸, at eachoccurrence, is independently selected from H, C₁-C₆ alkyl, phenyl,benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁹,at each occurrence, is independently selected from H, OH, methyl, ethyl,propyl, butyl, phenyl, benzyl, phenethyl; and R²⁰ is H or C₁-C₄ alkyl.13. A compound of claim 12, wherein: L is —NHC(═O)—, —C(═O)NH—, or—OC(═O)NH—; R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴; R⁴ isC₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenyl substituted with0-3 R^(4a), C₂-C₆ alkynyl substituted with 0-3 R^(4a), C₃-C₆ carbocyclesubstituted with 0-3 R^(4b), phenyl substituted with 0-3 R^(4b), or 5 to6 membered heterocycle containing 1 to 3 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycleis substituted with 0-3 R^(4b); R^(4a), at each occurrence, isindependently selected from is H, OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆carbocycle substituted with 0-3 R^(4b), phenyl substituted with 0-3R^(4b), or 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b); R^(4b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; RingC is a 3-6 membered carbocycle; wherein said 3-6 membered carbocyclicmoiety is saturated or partially unsaturated; wherein said 3-6 memberedcarbocyclic moiety is substituted with 0-2 R²¹; optionally, thecarbocycle contains a heteroatom selected from —O— and —N(R²⁰)—; R²¹, ateach occurrence, is independently selected from H, OH, Cl, F, Br, I, CN,NO₂, CF₃, acetyl, SCH₃, methyl, ethyl, methoxy, ethoxy, allyl, —OCF₃,and —SCF₃; R¹¹, at each occurrence, is independently selected from H,═O, NR¹⁸R¹⁹, CF₃; C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);phenyl substituted with 0-3 R^(11b); C₃-C₆ carbocycle substituted with0-3 R^(11b); and 5 to 7 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 7 membered heterocycle is substituted with 0-3 R^(11b); wherein said5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,homopiperidinyl, and tetrazolyl; R^(11a), at each occurrence, isindependently selected from H, methyl, ethyl, propyl, butyl, methoxy,ethoxy, propoxy, phenoxy, F, Cl, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substitutedwith 0-3 R^(11b); R^(11b), at each occurrence, is independently selectedfrom H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy,ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; W is a bond,—CH₂—, —CH₂CH₂—; X is a bond; phenyl substituted with 0-1 R^(Xb); C₃-C₆cycloalkyl substituted with 0-1 R^(Xb); or 5 to 6 membered heterocyclesubstituted with 0-1 R^(Xb); R^(Xb) is selected from H, OH, Cl, F,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl,methoxy, ethoxy, propoxy, and —OCF₃; Y is a bond, —C(═O)—, —O—, —S—,—S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—, or —N(CH₂CH₃)—; Z is H; C₁-C₈ alkylsubstituted with 0-3 R^(12a); C₂-C₆ alkenyl substituted with 0-3R^(12a); C₂-C₆ alkynyl substituted with 0-3 R^(12a); C₆-C₁₀ arylsubstituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4R^(12b); or 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b); R^(12a), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄haloalkyl-S—, C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀carbocycle substituted with 0-4 R^(12b); or 5 to 10 membered heterocyclecontaining 1 to 4 heteroatoms selected from nitrogen, oxygen, andsulphur, wherein said 5 to 10 membered heterocycle is substituted with0-3 R^(12b); R^(12b), at each occurrence, is independently selected fromH, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—; R¹³, at each occurrence, is independentlyselected from H, OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, and CF₃; R¹⁴ is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄alkoxyalkyl; R¹⁵, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, benzyl, and phenethyl; R¹⁶, at eachoccurrence, is independently selected from H, OH, methyl, ethyl, propyl,butyl, benzyl, phenethyl, methyl-C(═O)—, ethyl-C(═O)—, methyl-S(═O)₂—,and ethyl-S(═O)₂—; R¹⁸, at each occurrence, is independently selectedfrom H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;R¹⁹, at each occurrence, is independently selected from H, methyl,ethyl, propyl, and butyl; R²⁰ is H or C₁-C₄ alkyl.
 14. A compound ofclaim 13, wherein: L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; R³ is —R⁴,—CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴; R⁴ is C₁-C₆ alkyl substitutedwith 0-3 R^(4a), C₂-C₆ alkenyl substituted with 0-3 R^(4a), or C₂-C₆alkynyl substituted with 0-3 R^(4a); R^(4a), at each occurrence, isindependently selected from is H, OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆carbocycle substituted with 0-3 R^(4b), phenyl substituted with 0-3R^(4b), or 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b); wherein said 5 to 6membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl,furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl,pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl; R^(4b), ateach occurrence, is independently selected from H, OH, Cl, F, Br, I, CN,NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; RingC is a 3-6 membered carbocycle selected from:

 wherein said 3-6 membered carbocycle is substituted with 0-1 R²¹; R²¹is selected from H, OH, Cl, F, CN, CF₃, methyl, ethyl, methoxy, ethoxy,allyl, and —OCF₃; R¹¹, at each occurrence, is independently selectedfrom H, ═O, NR¹⁸R¹⁹; C₁-C₄ alkyl optionally substituted with 0-1R^(11a); phenyl substituted with 0-3 R^(11b); 5 to 7 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 7 membered heterocycle issubstituted with 0-3 R^(11b); wherein said 5 to 7 membered heterocycleis selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl,thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl,oxazolyl, isoxazolyl, homopiperidinyl, and tetrazolyl; R^(11a), at eachoccurrence, is independently selected from H, methyl, ethyl, propyl,methoxy, ethoxy, propoxy, phenoxy, F, Cl, ═O, NR¹⁵R¹⁶, CF₃, or phenylsubstituted with 0-3 R^(11b); R^(11b), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl,propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂haloalkoxy; W is a bond or —CH₂—; X is a bond, phenyl, C₃-C₆ cycloalkylor 5 to 6 membered heterocycle; Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—,—S(═O)₂—, —NH—, —N(CH₃)—, or —N(CH₂CH₃)—; Z is H; C₁-C₈ alkylsubstituted with 0-3 R^(12a); C₂-C₆ alkenyl substituted with 0-3R^(12a); C₂-C₆ alkynyl substituted with 0-3 R^(12a); C₆-C₁₀ arylsubstituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4R^(12b); or 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b); R^(12a), at eachoccurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, butyl,methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; phenylsubstituted with 0-4 R^(12b); C₃-6 carbocycle substituted with 0-4R^(12b); or 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(12b); R^(12b), at eachoccurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, butyl,methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; R¹³, ateach occurrence, is independently selected from H, OH, methyl, ethyl,propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN, NR¹⁵R¹⁶, and CF₃; R¹⁴ isH, phenyl, benzyl, methyl, ethyl, propyl, or butyl; R¹⁵, at eachoccurrence, is independently selected from H, methyl, ethyl, propyl, andbutyl; and R¹⁶, at each occurrence, is independently selected from H,OH, methyl, ethyl, propyl, butyl, benzyl, and phenethyl. R¹⁸, at eachoccurrence, is independently selected from H, methyl, ethyl, propyl,butyl, phenyl, benzyl, and phenethyl; R¹⁹, at each occurrence, isindependently selected from H, methyl, ethyl, propyl, and butyl; and R²⁰is H, methyl, or ethyl.
 15. A compound of claim 14, wherein: L is—NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; Ring C is selected from:

R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃,—CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂, —CH(OH)CH(CH₃)₂,—CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃, —CF₂CH₂CH(CH₃)₂,—CH(NHCH₃)CH₂CH(CH₃)₂, —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl-,cyclopentyl-, cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,1-NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,(4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,(3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,(3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,(2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,(2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,(3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,(2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,(2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,(3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,(3-F-5-Cl-phenyl)CH₂CH₂—, 4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—,phenyl-CH₂CH(OH)—, imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—; W is abond or —CH₂—; X is a bond;

Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or —N(CH₃)—, Zis methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl,t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl,3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl,2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl,2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl,3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl,3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl,2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl, furanyl, thienyl, pyridyl,2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl,isoxazolyl, 1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, morpholino, N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,(3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—,(4-Meo-phenyl)CH₂—, (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—,(4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—,4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—,(4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—,(2-Me-pyridyl)CH₂—, (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—,(1-imidazolyl)CH₂—, (oxazolyl)CH₂—, (isoxazolyl)CH₂—,(1-benzimidazolyl)CH₂—, (cyclopropyl)CH₂—, (cyclobutyl)CH₂—,(cyclopentyl)CH₂—, (cyclohexyl)CH₂—, (morpholino)CH₂—,(N-pipridinyl)CH₂—, phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—,(2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—,(2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,(2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,(3-Cl-4-F-phenyl)CH₂CH₂—, (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—,(4-MeO-phenyl)CH₂CH₂—, (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—,(4-Me-phenyl)CH₂CH₂—, (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—,(4-MeS-phenyl)CH₂CH₂—, (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,(4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—, (thienyl)CH₂CH₂—,(pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,(4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,(isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—,(cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—, (cyclohexyl)CH₂CH₂—,(morpholino)CH₂CH₂—, or (N-pipridinyl)CH₂CH₂—; R¹¹, at each occurrence,is independently selected from H, ═O, methyl, ethyl, phenyl, benzyl,phenethyl, 4-F-phenyl, (4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—,3-F-phenyl, (3-F-phenyl)CH₂—, (3-F-phenyl)CH₂CH₂—, 2-F-phenyl,(2-F-phenyl)CH₂—, (2-F-phenyl)CH₂CH₂—, 4-Cl-phenyl, (4-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂CH₂—, 3-Cl-phenyl, (3-Cl-phenyl)CH₂—,(3-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,(4-CH₃-phenyl)CH₂CH₂—, 3-CH₃-phenyl, (3-CH₃-phenyl)CH₂—,(3-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—,(4-CF₃-phenyl)CH₂CH₂—, cyclopentyl, pyrid-2-yl, pyrid-3-yl, orpyrid-4-yl; and R¹³, at each occurrence, is independently selected fromH, F, Cl, OH, —CH₃, —CH₂CH₃, —OCH₃, or —CF₃.
 16. A compound of claim 7of Formula (If):

or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof,wherein: L is —NHC(═O)—, —C((═O)NH—, or —OC(═O)NH—; R³ is —(CH₂)_(n)—R⁴,—(CH₂)_(l)—S—R⁴, —(CH₂)_(l)—O—R⁴, or —(CH₂)_(l)—N(R^(7b))—R⁴; n is 0, 1or 2; l is 1 or 2; R⁴ is C₁-C₈ alkyl substituted with 0-3 R^(4a), C₂-C₈alkenyl substituted with 0-3 R^(4a), C₂-C₈ alkynyl substituted with 0-3R^(4a), C₃-C₁₀ carbocycle substituted with 0-3 R^(4b), C₆-C₁₀ arylsubstituted with 0-3 R^(4b), or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(4b);R^(4a), at each occurrence, is independently selected from H, OH, F, Cl,Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),C₆-C₁₀ aryl substituted with 0-3 R^(4b), and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(4b); R^(4b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R^(7b) is H,methyl, or ethyl; Ring C is a 3-8 membered carbocycle; wherein said 3-8membered carbocyclic moiety is saturated or partially saturated; whereinsaid 3-8 membered carbocyclic moiety is substituted with 0-3 R²¹;optionally, the carbocycle contains a heteroatom selected from —O— and—N(R²⁰)—; R²¹, at each occurrence, is independently selected from H, OH,Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶,OR^(14a), C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹¹ is selectedfrom H, ═O, NR¹⁸R¹⁹, CF₃; C₁-C₄ alkyl optionally substituted with 0-1R^(11a); phenyl substituted with 0-3 R^(11b); C₃-C₆ carbocyclesubstituted with 0-3 R^(11b); and 5 to 7 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 7 membered heterocycle is substituted with 0-3 R^(11b);wherein said 5 to 7 membered heterocycle is selected from pyridinyl,pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,homopiperidinyl, and tetrazolyl; R^(11a), at each occurrence, isindependently selected from H, C₁-C₄ alkyl, OR¹⁴, F, Cl, ═O, NR¹⁵R¹⁶,CF₃, or phenyl substituted with 0-3 R^(11b); R^(11b), at eachoccurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃,methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl,and C₁-C₂ haloalkoxy; W is a bond, —CH₂—, —CH₂CH₂—; X is a bond; phenylsubstituted with 0-2 R^(Xb); C₃-C₆ cycloalkyl substituted with 0-2R^(Xb); or 5 to 6 membered heterocycle substituted with 0-2 R^(Xb);R^(Xb), at each occurrence, is independently selected from H, OH, Cl, F,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; Y is a bond, —C(═O)—,—O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—, —C(═O)NR^(19b)—, —NR^(19b)C(═O)—,—NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, —S(═O)NR^(19b)—,—C(═O)O—, or —OC(═O)—; Z is H; C₁-C₈ alkyl substituted with 0-3 R^(12a);C₂-C₆ alkenyl substituted with 0-3 R^(12a); C₂-C₆ alkynyl substitutedwith 0-3 R^(12a); C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀carbocycle substituted with 0-4 R^(12b); or 5 to 10 membered heterocyclecontaining 1 to 4 heteroatoms selected from nitrogen, oxygen, andsulphur, wherein said 5 to 10 membered heterocycle is substituted with0-3 R^(12b); R^(12a), at each occurrence, is independently selected fromH, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄haloalkoxy, C₁-C₄ haloalkyl-S—, C₆-C₁₀ aryl substituted with 0-4R^(12b); C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and 5 to 10membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycleis substituted with 0-3 R^(12b); R^(12b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹⁴ is H, phenyl,benzyl, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆ cycloalkyl; R^(14a) isH, phenyl, benzyl, or C₁-C₄ alkyl; R¹⁵, at each occurrence, isindependently selected from H, C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₆alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁶, at each occurrence, isindependently selected from H, OH, C₁-C₆ alkyl, benzyl, phenethyl,(C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄ alkyl)-S(═O)₂—; R¹⁸, at eachoccurrence, is independently selected from H, C₁-C₆ alkyl, phenyl,benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁹,at each occurrence, is independently selected from H, OH, methyl, ethyl,propyl, butyl, phenyl, benzyl, phenethyl; and R²⁰ is H or C₁-C₄ alkyl.17. A compound of claim 16, wherein: L is —NHC(═O)—, —C(═O)NH—, or—OC(═O)NH—; R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴; R⁴ isC₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenyl substituted with0-3 R^(4a), C₂-C₆ alkynyl substituted with 0-3 R^(4a), C₃-C₆ carbocyclesubstituted with 0-3 R^(4b), phenyl substituted with 0-3 R^(4b), or 5 to6 membered heterocycle containing 1 to 3 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycleis substituted with 0-3 R^(4b); R^(4a), at each occurrence, isindependently selected from is H, OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆carbocycle substituted with 0-3 R^(4b), phenyl substituted with 0-3R^(4b), or 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b); R^(4b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; RingC is a 3-6 membered carbocycle; wherein said 3-6 membered carbocyclicmoiety is saturated or partially unsaturated; wherein said 3-6 memberedcarbocyclic moiety is substituted with 0-2 R²¹; optionally, thecarbocycle contains a heteroatom selected from —O— and —N(R²⁰)—; R²¹, ateach occurrence, is independently selected from H, OH, Cl, F, Br, I, CN,NO₂, CF₃, acetyl, SCH₃, methyl, ethyl, methoxy, ethoxy, allyl, —OCF₃,and —SCF₃; R¹¹ is selected from H, ═O, NR¹⁸R¹⁹, CF₃; C₁-C₄ alkyloptionally substituted with 0-1 R^(11a); phenyl substituted with 0-3R^(11b); C₃-C₆ carbocycle substituted with 0-3 R^(11b); and 5 to 7membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycleis substituted with 0-3 R^(11b); wherein said 5 to 7 memberedheterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl,thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl,imidazolyl, oxazolyl, isoxazolyl, homopiperidinyl, and tetrazolyl;R^(11a), at each occurrence, is independently selected from H, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, phenoxy, F, Cl, ═O,NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b); R^(11b), at eachoccurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃,methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl,and C₁-C₂ haloalkoxy; W is a bond, —CH₂—, —CH₂CH₂—; X is a bond; phenylsubstituted with 0-1 R^(Xb); C₃-C₆ cycloalkyl substituted with 0-1R^(Xb); or 5 to 6 membered heterocycle substituted with 0-1 R^(Xb);R^(Xb) is selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, methoxy, ethoxy, propoxy,and —OCF₃; Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—,—N(CH₃)—, or —N(CH₂CH₃)—; Z is H; C₁-C₈ alkyl substituted with 0-3R^(12a); C₂-C₆ alkenyl substituted with 0-3 R^(12a); C₂-C₆ alkynylsubstituted with 0-3 R^(12a); C₆-C₁₀ aryl substituted with 0-4 R^(12b);C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(12b); R^(12a), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶,—C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl,C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substitutedwith 0-4 R^(12b); or 5 to 10 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 10 membered heterocycle is substituted with 0-3 R^(12b); R^(12b), ateach occurrence, is independently selected from H, OH, Cl, F, Br, I, CN,NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹⁴is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl; R¹⁵, at eachoccurrence, is independently selected from H, methyl, ethyl, propyl,butyl, benzyl, and phenethyl; R¹⁶, at each occurrence, is independentlyselected from H, OH, methyl, ethyl, propyl, butyl, benzyl, phenethyl,methyl-C(═O)—, ethyl-C(═O)—, methyl-S(═O)₂—, and ethyl-S(═O)₂—; R¹⁸, ateach occurrence, is independently selected from H, methyl, ethyl,propyl, butyl, phenyl, benzyl, and phenethyl; R¹⁹, at each occurrence,is independently selected from H, methyl, ethyl, propyl, and butyl; R²⁰is H or C₁-C₄ alkyl.
 18. A compound of claim 17, wherein: L is—NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴,—CH₂OR⁴, or —CH₂CH₂OR⁴; R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a),C₂-C₆ alkenyl substituted with 0-3 R^(4a), or C₂-C₆ alkynyl substitutedwith 0-3 R^(4a); R^(4a), at each occurrence, is independently selectedfrom is H, OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆ carbocycle substitutedwith 0-3 R^(4b), phenyl substituted with 0-3 R^(4b), or 5 to 6 memberedheterocycle containing 1 to 3 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 6 membered heterocycle issubstituted with 0-3 R^(4b); wherein said 5 to 6 membered heterocycle isselected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl,thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl,oxazolyl, isoxazolyl, and tetrazolyl; R^(4b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; Ring C is a 3-6membered carbocycle selected from:

 wherein said 3-6 membered carbocycle is substituted with 0-1 R²¹; R²¹is selected from H, OH, Cl, F, CN, CF₃, methyl, ethyl, methoxy, ethoxy,allyl, and —OCF₃; R¹¹ is selected from H, ═O, NR¹⁸R¹⁹; C₁-C₄ alkyloptionally substituted with 0-1 R^(11a); phenyl substituted with 0-3R^(11b); 5 to 7 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 7membered heterocycle is substituted with 0-3 R^(11b); wherein said 5 to7 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,homopiperidinyl, and tetrazolyl; R^(11a), at each occurrence, isindependently selected from H, methyl, ethyl, propyl, methoxy, ethoxy,propoxy, phenoxy, F, Cl, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with0-3 R^(11b); R^(11b), at each occurrence, is independently selected fromH, OH, Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy,ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; W is a bond or—CH₂—; X is a bond, phenyl, C₃-C₆ cycloalkyl or 5 to 6 memberedheterocycle; Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—,—N(CH₃)—, or —N(CH₂CH₃)—; Z is H; C₁-C₈ alkyl substituted with 0-3R^(12a); C₂-C₆ alkenyl substituted with 0-3 R^(12a); C₂-C₆ alkynylsubstituted with 0-3 R^(12a); C₆-C₁₀ aryl substituted with 0-4 R^(12b);C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(12b); R^(12a), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; phenyl substituted with0-4 R^(12b); C₃-6 carbocycle substituted with 0-4 R^(12b); or 5 to 6membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycleis substituted with 0-3 R^(12b); R^(12b), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; R¹⁴ is H, phenyl,benzyl, methyl, ethyl, propyl, or butyl; R¹⁵, at each occurrence, isindependently selected from H, methyl, ethyl, propyl, and butyl; andR¹⁶, at each occurrence, is independently selected from H, OH, methyl,ethyl, propyl, butyl, benzyl, and phenethyl. R¹⁸, at each occurrence, isindependently selected from H, methyl, ethyl, propyl, butyl, phenyl,benzyl, and phenethyl; R¹⁹, at each occurrence, is independentlyselected from H, methyl, ethyl, propyl, and butyl; and R²⁰ is H, methyl,or ethyl.
 19. A compound of claim 18, wherein: L is —NHC(═O)—,—C(═O)NH—, or —OC(═O)NH—; Ring C is selected from:

R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃,—CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂, —CH(OH)CH(CH₃)₂,—CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃, —CF₂CH₂CH(CH₃)₂,—CH(NHCH₃)CH₂CH(CH₃)₂, —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl-,cyclopentyl-, cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,1-NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,(4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,(3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,(3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,(2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,(2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,(3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,(2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,(2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,(3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,(3-F-5-Cl-phenyl)CH₂CH₂—, 4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—,phenyl-CH₂CH(OH)—, imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—; W is abond or —CH₂—; X is a bond;

Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or —N(CH₃)—, Zis methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl,t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl,3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl,2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl,2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl,3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl,3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl,2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl, furanyl, thienyl, pyridyl,2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl,isoxazolyl, 1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, morpholino, N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,(3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—,(4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—,(4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—,4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—,(4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—,(2-Me-pyridyl)CH₂—, (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—,(1-imidazolyl)CH₂—, (oxazolyl)CH₂—, (isoxazolyl)CH₂—,(1-benzimidazolyl)CH₂—, (cyclopropyl)CH₂—, (cyclobutyl)CH₂—,(cyclopentyl)CH₂—, (cyclohexyl)CH₂—, (morpholino)CH₂—,(N-pipridinyl)CH₂—, phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—,(2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—,(2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,(2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,(3-Cl-4-F-phenyl)CH₂CH₂—, (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—,(4-MeO-phenyl)CH₂CH₂—, (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—,(4-Me-phenyl)CH₂CH₂—, (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—,(4-MeS-phenyl)CH₂CH₂—, (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,(4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—, (thienyl)CH₂CH₂—,(pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,(4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,(isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—,(cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—, (cyclohexyl)CH₂CH₂—,(morpholino)CH₂CH₂—, or (N-pipridinyl)CH₂CH₂—; and R¹¹, at eachoccurrence, is independently selected from H, ═O, methyl, ethyl, phenyl,benzyl, phenethyl, 4-F-phenyl, (4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—,3-F-phenyl, (3-F-phenyl)CH₂—, (3-F-phenyl)CH₂CH₂—, 2-F-phenyl,(2-F-phenyl)CH₂—, (2-F-phenyl)CH₂CH₂—, 4-Cl-phenyl, (4-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂CH₂—, 3-Cl-phenyl, (3-Cl-phenyl)CH₂—,(3-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,(4-CH₃-phenyl)CH₂CH₂—, 3-CH₃-phenyl, (3-CH₃-phenyl)CH₂—,(3-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—,(4-CF₃-phenyl)CH₂CH₂—, cyclopentyl, pyrid-2-yl, pyrid-3-yl, orpyrid-4-yl.
 20. A compound of claim 1 selected from:{[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carboxamide;{[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide;[(N-butylcarbamoyl)cyclopentyl]-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide;2-(3,5-difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclohexyl}acetamide;2-(3,5-difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}acetamide;2-(3,5-difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopropyl}acetamide;3-cyclopentyl-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclohexyl}propanamide;2-(3,5-difluorophenyl)-N-{4-[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl](4-piperidyl)}acetamide;phenyl4-[2-(3,5-difluorophenyl)acetylamino]-4-[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]piperidinecarboxylate;4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}{[(phenylmethoxy)carbonylamino]cyclopentyl}carboxamide;(2S)-N-{[N-(1-{[3-(4-fluorophenoxy)phenyl]methyl}-2-oxoazaperhydroepin-3-yl)carbamoyl]cyclopropyl}-2-hydroxy-4-methylpentanamide;(2S)-N-{[N-(1-{[3-(4-fluorophenoxy)phenyl]methyl}-2-oxoazaperhydroepin-3-yl)carbamoyl]cyclopentyl}-2-hydroxy-3-methylbutanamide;2,2-difluoro-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-4-phenylbutanamide;N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-3-(4-piperidyl)propanamide;(2S)-2-hydroxy-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide;3-cyclopropyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide;(2R)-2-hydroxy-3-imidazol-2-yl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide;2-ethoxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide;3-cyclopentyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide;(2S)-2-hydroxy-3-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]butanamide;(2S)-2-cyclohexyl-2-hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide;(2R)-2-cyclohexyl-2-hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide;(2S)-2-amino-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide;[(cyclohexylcarbonylamino)cyclopentyl]-N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carboxamide;{[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carboxamide;4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide;(2S)-2-hydroxy-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide;3-methoxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide;(2S)-2-hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-3-phenylpropanamide;N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-2-(phenylmethoxy)acetamide;(2S)-2-hydroxy-3-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}butanamide;(2S)-2-hydroxy-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;3-cyclopentyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}propanamide;(2S)-2-cyclohexyl-2-hydroxy-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}acetamide;3-cyclopropyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}propanamide;N-{[N-(1-butyl-5-cyclopentyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}-4-methylpentanamide;N-{[N-(5-cyclopentyl-1-methyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}-4-methylpentanamide;(2S)-2-hydroxy-3-methyl-N-({N-[2-oxo-1-benzyl(3H,4H,5H-benzo[f]azaperhydroepin-3-yl)]carbamoyl}cyclopentyl)butanamide;(2S)-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-2-[(propylsulfonyl)amino]pentanamide;(2S)-2-amino-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;2,2-difluoro-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;4-methyl-N-{[N-(6-oxo(5H,7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;N-({N-[5-(3,3-dimethyl-2-oxobutyl)-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide;4-methyl-N-[(N-{6-oxo-5-[(3-phenoxyphenyl)methyl](7H-dibenzo[d,f]azaperhydroepin-7-yl)}carbamoyl)cyclopentyl]pentanamide;N-{[N-(5-butyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-4-methylpentanamide;4-methyl-N-({N-[6-oxo-5-benzyl(7H-dibenzo[d,f]azaperhydroepin-7-yl)]carbamoyl}cyclopentyl)pentanamide;N-({N-[5-(tert-butyl)-1-methyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide;N-({N-[5-(tert-butyl)-1-butyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide;andN-({N-[5-butyl-2-oxo-1-(2-pyridylmethyl)(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide.21. A method for the treatment of neurological disorders associated withβ-amyloid production comprising administering to a host in need of suchtreatment a therapeutically effective amount of a compound of claim 1 ora pharmaceutically acceptable salt or prodrug thereof.
 22. Apharmaceutical composition comprising a compound of claim 1 and apharmaceutically acceptable carrier.
 23. A method for the treatment ofneurological disorders associated with β-amyloid production comprisingadministering to a host in need of such treatment a therapeuticallyeffective amount of a compound of claim
 1. 24. A method for inhibitingγ-secretase activity comprising administering to a host in need of suchinhibition a therapeutically effective amount of a compound of claim 1that inhibits γ-secretase activity.